TBD Meeting (3035-20)

Tandem autologous hematopoietic stem cell transplantation (HSCT) could extend progression-free survival (PFS) for some patients with newly diagnosed multiple myeloma, based on long-term data from the phase 3 STaMINA trial.

While the intent-to-treat analysis showed no difference in 6-year PFS rate between single versus tandem HSCT, the as-treated analysis showed that patients who received two transplants had a 6-year PFS rate that was approximately 10% higher than those who received just one transplant, reported lead author Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

The STaMINA trial, also known as BMT CTN 0702, involved 758 patients who were randomized to receive one of three treatment regimens followed by 3 years of maintenance lenalidomide: tandem HSCT (auto/auto), single HSCT plus consolidation with lenalidomide/bortezomib/dexamethasone (auto/RVD), and single HSCT (auto/len).

“At the time, we intended the study to stop approximately 38 months from randomization, allowing for the time for transplant, and then 3 years of maintenance,” Dr. Hari said. However, as the results of lenalidomide maintenance in CALGB 00104 study were reported, they allowed for a follow-on protocol, which provided patients who are progression-free at the completion of the original STaMINA trial to go on to a second follow-on trial, which allowed lenalidomide maintenance on an indefinite basis, he added.

The present analysis looked at the long-term results of this follow-on trial, including the impact of discontinuing lenalidomide.

Aligning with the original study, the present intent-to-treat analysis showed no significant difference between treatment arms for 6-year PFS rate or overall survival. Respectively, PFS rates for auto/auto, auto/RVD, and auto/len were 43.9%, 39.7%, and 40.9% (P = .6).

But 32% of patients in the tandem group never underwent second HSCT, Dr. Hari noted, prompting the as-treated analysis. Although overall survival remained similar between groups, the 6-year PFS was significantly higher for patients who underwent tandem HSCT, at 49.4%, compared with 39.7% for auto/RVD and 38.6% for auto/len (P = .03).

Subgroup analysis showed the statistical benefit of tandem HSCT was driven by high-risk patients, who had a significantly better PFS after tandem transplant, compared with standard-risk patients, who showed no significant benefit.

Dr. Hari called the findings “provocative.”

“The tandem auto approach may still be relevant in high-risk multiple myeloma patients,” he said.

Dr. Hari and his colleagues also found that patients who stayed on maintenance lenalidomide after 38 months had a better 5-year PFS rate than those who discontinued maintenance therapy (79.5% vs. 61%; P = .0004). Subgroup analysis showed this benefit was statistically significant among patients with standard-risk disease (86.3% vs. 66%; P less than .001) but not among those in the high-risk subgroup (86.7% vs. 67.8%; P = .2).

However, Dr. Hari suggested that, based on the similarity of proportions between subgroups, the lack of significance in the high-risk subgroup was likely because of small sample size, suggesting the benefit of maintenance was actually shared across risk strata.

“Lenalidomide maintenance becomes a significant factor for preventing patients from progression,” Dr. Hari said, noting that the tandem transplant approach requires further study, and that he and his colleagues would soon publish minimal residual disease data.

He finished his presentation with a clear clinical recommendation. “Preplanned lenalidomide discontinuation at 3 years is not recommended based on inferior progression-free survival among those who stopped such therapy,” he said.

Invited discussant Joshua R. Richter, MD, of the Icahn School of Medicine at Mount Sinai, New York, said the findings encourage high-dose maintenance therapy, and for some, tandem HSCT.

“The STaMINA study presented today supports the notion that some patients with high-risk disease still may benefit and have further tumor burden reduction with the second transplant that leads to deeper remissions and hopefully abrogates diminished outcomes,” Dr. Richter said during a virtual presentation.

But improvements are needed to better identify such patients, Dr. Richter added. He highlighted a lack of standardization in risk modeling, with various factors currently employed, such as patient characteristics and genomic markers, among several others.

“Better definitions will allow us to cross compare and make true analyses about how to manage these patients,” Dr. Richter said. “Despite the improvements across the board that we’ve seen in myeloma patients, high-risk disease continues to represent a more complicated arena. And patients continue to suffer from worse outcomes, despite all of the other advances.”

The study was funded by the National Institutes of Health. The investigators disclosed additional relationships with Amgen, Celgene, Novartis, and others. Dr. Richter disclosed affiliations with Takeda, Sanofi, Janssen, and others.
 

SOURCE: Hari et al. ASCO 2020. Abstract 8506.

Tandem autologous hematopoietic stem cell transplantation (HSCT) could extend progression-free survival (PFS) for some patients with newly diagnosed multiple myeloma, based on long-term data from the phase 3 STaMINA trial.

While the intent-to-treat analysis showed no difference in 6-year PFS rate between single versus tandem HSCT, the as-treated analysis showed that patients who received two transplants had a 6-year PFS rate that was approximately 10% higher than those who received just one transplant, reported lead author Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

The STaMINA trial, also known as BMT CTN 0702, involved 758 patients who were randomized to receive one of three treatment regimens followed by 3 years of maintenance lenalidomide: tandem HSCT (auto/auto), single HSCT plus consolidation with lenalidomide/bortezomib/dexamethasone (auto/RVD), and single HSCT (auto/len).

“At the time, we intended the study to stop approximately 38 months from randomization, allowing for the time for transplant, and then 3 years of maintenance,” Dr. Hari said. However, as the results of lenalidomide maintenance in CALGB 00104 study were reported, they allowed for a follow-on protocol, which provided patients who are progression-free at the completion of the original STaMINA trial to go on to a second follow-on trial, which allowed lenalidomide maintenance on an indefinite basis, he added.

The present analysis looked at the long-term results of this follow-on trial, including the impact of discontinuing lenalidomide.

Aligning with the original study, the present intent-to-treat analysis showed no significant difference between treatment arms for 6-year PFS rate or overall survival. Respectively, PFS rates for auto/auto, auto/RVD, and auto/len were 43.9%, 39.7%, and 40.9% (P = .6).

But 32% of patients in the tandem group never underwent second HSCT, Dr. Hari noted, prompting the as-treated analysis. Although overall survival remained similar between groups, the 6-year PFS was significantly higher for patients who underwent tandem HSCT, at 49.4%, compared with 39.7% for auto/RVD and 38.6% for auto/len (P = .03).

Subgroup analysis showed the statistical benefit of tandem HSCT was driven by high-risk patients, who had a significantly better PFS after tandem transplant, compared with standard-risk patients, who showed no significant benefit.

Dr. Hari called the findings “provocative.”

“The tandem auto approach may still be relevant in high-risk multiple myeloma patients,” he said.

Dr. Hari and his colleagues also found that patients who stayed on maintenance lenalidomide after 38 months had a better 5-year PFS rate than those who discontinued maintenance therapy (79.5% vs. 61%; P = .0004). Subgroup analysis showed this benefit was statistically significant among patients with standard-risk disease (86.3% vs. 66%; P less than .001) but not among those in the high-risk subgroup (86.7% vs. 67.8%; P = .2).

However, Dr. Hari suggested that, based on the similarity of proportions between subgroups, the lack of significance in the high-risk subgroup was likely because of small sample size, suggesting the benefit of maintenance was actually shared across risk strata.

“Lenalidomide maintenance becomes a significant factor for preventing patients from progression,” Dr. Hari said, noting that the tandem transplant approach requires further study, and that he and his colleagues would soon publish minimal residual disease data.

He finished his presentation with a clear clinical recommendation. “Preplanned lenalidomide discontinuation at 3 years is not recommended based on inferior progression-free survival among those who stopped such therapy,” he said.

Invited discussant Joshua R. Richter, MD, of the Icahn School of Medicine at Mount Sinai, New York, said the findings encourage high-dose maintenance therapy, and for some, tandem HSCT.

“The STaMINA study presented today supports the notion that some patients with high-risk disease still may benefit and have further tumor burden reduction with the second transplant that leads to deeper remissions and hopefully abrogates diminished outcomes,” Dr. Richter said during a virtual presentation.

But improvements are needed to better identify such patients, Dr. Richter added. He highlighted a lack of standardization in risk modeling, with various factors currently employed, such as patient characteristics and genomic markers, among several others.

“Better definitions will allow us to cross compare and make true analyses about how to manage these patients,” Dr. Richter said. “Despite the improvements across the board that we’ve seen in myeloma patients, high-risk disease continues to represent a more complicated arena. And patients continue to suffer from worse outcomes, despite all of the other advances.”

The study was funded by the National Institutes of Health. The investigators disclosed additional relationships with Amgen, Celgene, Novartis, and others. Dr. Richter disclosed affiliations with Takeda, Sanofi, Janssen, and others.
 

SOURCE: Hari et al. ASCO 2020. Abstract 8506.

Tandem autologous hematopoietic stem cell transplantation (HSCT) could extend progression-free survival (PFS) for some patients with newly diagnosed multiple myeloma, based on long-term data from the phase 3 STaMINA trial.

While the intent-to-treat analysis showed no difference in 6-year PFS rate between single versus tandem HSCT, the as-treated analysis showed that patients who received two transplants had a 6-year PFS rate that was approximately 10% higher than those who received just one transplant, reported lead author Parameswaran Hari, MD, of the Medical College of Wisconsin, Milwaukee, who presented the findings as part of the American Society of Clinical Oncology virtual scientific program.

The STaMINA trial, also known as BMT CTN 0702, involved 758 patients who were randomized to receive one of three treatment regimens followed by 3 years of maintenance lenalidomide: tandem HSCT (auto/auto), single HSCT plus consolidation with lenalidomide/bortezomib/dexamethasone (auto/RVD), and single HSCT (auto/len).

“At the time, we intended the study to stop approximately 38 months from randomization, allowing for the time for transplant, and then 3 years of maintenance,” Dr. Hari said. However, as the results of lenalidomide maintenance in CALGB 00104 study were reported, they allowed for a follow-on protocol, which provided patients who are progression-free at the completion of the original STaMINA trial to go on to a second follow-on trial, which allowed lenalidomide maintenance on an indefinite basis, he added.

The present analysis looked at the long-term results of this follow-on trial, including the impact of discontinuing lenalidomide.

Aligning with the original study, the present intent-to-treat analysis showed no significant difference between treatment arms for 6-year PFS rate or overall survival. Respectively, PFS rates for auto/auto, auto/RVD, and auto/len were 43.9%, 39.7%, and 40.9% (P = .6).

But 32% of patients in the tandem group never underwent second HSCT, Dr. Hari noted, prompting the as-treated analysis. Although overall survival remained similar between groups, the 6-year PFS was significantly higher for patients who underwent tandem HSCT, at 49.4%, compared with 39.7% for auto/RVD and 38.6% for auto/len (P = .03).

Subgroup analysis showed the statistical benefit of tandem HSCT was driven by high-risk patients, who had a significantly better PFS after tandem transplant, compared with standard-risk patients, who showed no significant benefit.

Dr. Hari called the findings “provocative.”

“The tandem auto approach may still be relevant in high-risk multiple myeloma patients,” he said.

Dr. Hari and his colleagues also found that patients who stayed on maintenance lenalidomide after 38 months had a better 5-year PFS rate than those who discontinued maintenance therapy (79.5% vs. 61%; P = .0004). Subgroup analysis showed this benefit was statistically significant among patients with standard-risk disease (86.3% vs. 66%; P less than .001) but not among those in the high-risk subgroup (86.7% vs. 67.8%; P = .2).

However, Dr. Hari suggested that, based on the similarity of proportions between subgroups, the lack of significance in the high-risk subgroup was likely because of small sample size, suggesting the benefit of maintenance was actually shared across risk strata.

“Lenalidomide maintenance becomes a significant factor for preventing patients from progression,” Dr. Hari said, noting that the tandem transplant approach requires further study, and that he and his colleagues would soon publish minimal residual disease data.

He finished his presentation with a clear clinical recommendation. “Preplanned lenalidomide discontinuation at 3 years is not recommended based on inferior progression-free survival among those who stopped such therapy,” he said.

Invited discussant Joshua R. Richter, MD, of the Icahn School of Medicine at Mount Sinai, New York, said the findings encourage high-dose maintenance therapy, and for some, tandem HSCT.

“The STaMINA study presented today supports the notion that some patients with high-risk disease still may benefit and have further tumor burden reduction with the second transplant that leads to deeper remissions and hopefully abrogates diminished outcomes,” Dr. Richter said during a virtual presentation.

But improvements are needed to better identify such patients, Dr. Richter added. He highlighted a lack of standardization in risk modeling, with various factors currently employed, such as patient characteristics and genomic markers, among several others.

“Better definitions will allow us to cross compare and make true analyses about how to manage these patients,” Dr. Richter said. “Despite the improvements across the board that we’ve seen in myeloma patients, high-risk disease continues to represent a more complicated arena. And patients continue to suffer from worse outcomes, despite all of the other advances.”

The study was funded by the National Institutes of Health. The investigators disclosed additional relationships with Amgen, Celgene, Novartis, and others. Dr. Richter disclosed affiliations with Takeda, Sanofi, Janssen, and others.
 

SOURCE: Hari et al. ASCO 2020. Abstract 8506.

Adjuvant gefitinib provides no overall survival (OS) benefit over standard chemotherapy for EGFR-mutant, resected, stage II-IIIA non–small cell lung cancer (NSCLC), according to final results from the phase 3 ADJUVANT trial.

The median OS was 75.5 months in patients randomized to adjuvant gefitinib and 62.8 months in patients randomized to vinorelbine plus cisplatin.

Yi-Long Wu, MD, of Guangdong Lung Cancer Institute in Guangzhou, China, reported these results as part of the American Society of Clinical Oncology virtual scientific program.

Prior results from this trial had shown a disease-free survival (DFS) benefit with gefitinib, but this did not translate to an OS benefit at the final analysis, Dr. Wu said.

He noted, however, that the median OS of 75.5 months in the gefitinib arm “was one of the best in resected EGFR-mutant non–small cell lung cancer, compared with historical data.”

The findings also suggest a possible benefit with at least 18 months of gefitinib and show that adjuvant EGFR tyrosine kinase inhibitors (TKIs) should be considered the optimal therapy to improve DFS and achieve potentially better OS in this setting, Dr. Wu said.
 

Study details and DFS

The ADJUVANT trial (NCT01405079) randomized 222 patients, aged 18-75 years, with EGFR-mutant, stage II-IIIA (N1-N2) NSCLC who had undergone complete resection. Patients were enrolled at 27 sites between September 2011 and April 2014.

The patients were randomized 1:1 to receive 250 mg of gefitinib once daily for 24 months, or 25 mg/m² of vinorelbine on days 1 and 8 plus 75 mg/m² of cisplatin on day 1 every 3 weeks for 4 cycles.

The intent-to-treat (ITT) population included 111 patients in each arm. The per-protocol population included 106 patients in the gefitinib arm and 87 patients in the chemotherapy arm.

Primary results from this trial showed a significant improvement in DFS with gefitinib (Lancet Oncol. 2018 Jan;19[1]:139-48). That improvement was maintained in the final analysis.

The median DFS was 30.8 months in the gefitinib arm and 19.8 months in the chemotherapy arm for both the ITT and per-protocol populations. The hazard ratio (HR) was 0.56 (P = .001) in the ITT population and 0.51 (P < .001) in the per-protocol population.

In the ITT population, the 5-year DFS rates were 22.6% in the gefitinib arm and 23.2% in the chemotherapy arm. In the per-protocol population, the 5-year DFS rates were 22.6% and 22.8%, respectively.

OS results

The median OS was 75.5 months in the gefitinib arm and 62.8 months in the chemotherapy arm for both the ITT and per-protocol populations. The HR was 0.92 in both the ITT (P = .674) and per-protocol populations (P = .686).

In the ITT population, the 5-year OS rates were 53.2% in the gefitinib arm and 51.2% in the chemotherapy arm. In the per-protocol population, the 5-year OS rates were 53.2% and 50.7%, respectively.

Subgroup analyses by age, gender, lymph node status, and EGFR mutation showed trends toward improved OS with gefitinib, but the differences were not statistically significant.

The researchers conducted a post hoc analysis to assess the effect of subsequent treatment on patient outcomes. The analysis showed that patients who received gefitinib with subsequent EGFR-TKIs had the best responses and OS.

The median OS was not reached among patients who received gefitinib and subsequent EGFR-TKIs, whereas the median OS ranged from 15.6 months to 62.8 months in other groups. The shortest OS was observed in patients who received adjuvant chemotherapy without subsequent therapy.

The duration of gefitinib treatment also appeared to affect OS. The median OS was 35.7 months in patients who received gefitinib for less than 18 months, and the median OS was not reached in patients who received gefitinib for 18 months or longer (HR, 0.38; P < .001).
 

Implications and potential next steps

Despite the lack of OS improvement with gefitinib, “all of the patients on this study did much, much better than historical non–small cell lung cancer not specified by the EGFR mutation, with 70 months median survival compared to 35 months median survival for N2-positive disease,” said invited discussant Christopher G. Azzoli, MD, director of thoracic oncology at Lifespan Cancer Institute at Brown University in Providence, R.I.

“But you can’t avoid noticing how the curves come back together in terms of disease-free survival when your effective treatment is limited to 24 months,” he added.

An apparent risk of late brain recurrence in the gefitinib arm is also a concern, Dr. Azzoli said. “So ... longer duration of treatment with a drug that has better control of CNS [central nervous system] disease, such as osimertinib, may improve both DFS and OS,” he added.

Only about 50% of patients in the chemotherapy arm received a TKI at recurrence. The post hoc analysis showing that TKI recipients had the best outcomes raises the question of whether “the survival benefit could be conferred by delivering a superior drug merely at recurrence, or is there benefit to earlier delivery of an effective drug,” Dr. Azzoli said.

Given the high cost of continuous therapy, biomarker refinement could help improve treatment decision-making, he said, noting that “early testing of blood DNA to detect cancer in the body as minimal residual disease is showing promise,” and that many phase 3 studies of EGFR-TKIs are ongoing.

The current trial was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu disclosed relationships with AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/China, Lilly, MSD Oncology, Pfizer, and Roche. Dr. Azzoli reported having no disclosures.

sworcester@mdedge.com

SOURCE: Wu Y et al. ASCO 2020, Abstract 9005.

Adjuvant gefitinib provides no overall survival (OS) benefit over standard chemotherapy for EGFR-mutant, resected, stage II-IIIA non–small cell lung cancer (NSCLC), according to final results from the phase 3 ADJUVANT trial.

The median OS was 75.5 months in patients randomized to adjuvant gefitinib and 62.8 months in patients randomized to vinorelbine plus cisplatin.

Yi-Long Wu, MD, of Guangdong Lung Cancer Institute in Guangzhou, China, reported these results as part of the American Society of Clinical Oncology virtual scientific program.

Prior results from this trial had shown a disease-free survival (DFS) benefit with gefitinib, but this did not translate to an OS benefit at the final analysis, Dr. Wu said.

He noted, however, that the median OS of 75.5 months in the gefitinib arm “was one of the best in resected EGFR-mutant non–small cell lung cancer, compared with historical data.”

The findings also suggest a possible benefit with at least 18 months of gefitinib and show that adjuvant EGFR tyrosine kinase inhibitors (TKIs) should be considered the optimal therapy to improve DFS and achieve potentially better OS in this setting, Dr. Wu said.
 

Study details and DFS

The ADJUVANT trial (NCT01405079) randomized 222 patients, aged 18-75 years, with EGFR-mutant, stage II-IIIA (N1-N2) NSCLC who had undergone complete resection. Patients were enrolled at 27 sites between September 2011 and April 2014.

The patients were randomized 1:1 to receive 250 mg of gefitinib once daily for 24 months, or 25 mg/m² of vinorelbine on days 1 and 8 plus 75 mg/m² of cisplatin on day 1 every 3 weeks for 4 cycles.

The intent-to-treat (ITT) population included 111 patients in each arm. The per-protocol population included 106 patients in the gefitinib arm and 87 patients in the chemotherapy arm.

Primary results from this trial showed a significant improvement in DFS with gefitinib (Lancet Oncol. 2018 Jan;19[1]:139-48). That improvement was maintained in the final analysis.

The median DFS was 30.8 months in the gefitinib arm and 19.8 months in the chemotherapy arm for both the ITT and per-protocol populations. The hazard ratio (HR) was 0.56 (P = .001) in the ITT population and 0.51 (P < .001) in the per-protocol population.

In the ITT population, the 5-year DFS rates were 22.6% in the gefitinib arm and 23.2% in the chemotherapy arm. In the per-protocol population, the 5-year DFS rates were 22.6% and 22.8%, respectively.

OS results

The median OS was 75.5 months in the gefitinib arm and 62.8 months in the chemotherapy arm for both the ITT and per-protocol populations. The HR was 0.92 in both the ITT (P = .674) and per-protocol populations (P = .686).

In the ITT population, the 5-year OS rates were 53.2% in the gefitinib arm and 51.2% in the chemotherapy arm. In the per-protocol population, the 5-year OS rates were 53.2% and 50.7%, respectively.

Subgroup analyses by age, gender, lymph node status, and EGFR mutation showed trends toward improved OS with gefitinib, but the differences were not statistically significant.

The researchers conducted a post hoc analysis to assess the effect of subsequent treatment on patient outcomes. The analysis showed that patients who received gefitinib with subsequent EGFR-TKIs had the best responses and OS.

The median OS was not reached among patients who received gefitinib and subsequent EGFR-TKIs, whereas the median OS ranged from 15.6 months to 62.8 months in other groups. The shortest OS was observed in patients who received adjuvant chemotherapy without subsequent therapy.

The duration of gefitinib treatment also appeared to affect OS. The median OS was 35.7 months in patients who received gefitinib for less than 18 months, and the median OS was not reached in patients who received gefitinib for 18 months or longer (HR, 0.38; P < .001).
 

Implications and potential next steps

Despite the lack of OS improvement with gefitinib, “all of the patients on this study did much, much better than historical non–small cell lung cancer not specified by the EGFR mutation, with 70 months median survival compared to 35 months median survival for N2-positive disease,” said invited discussant Christopher G. Azzoli, MD, director of thoracic oncology at Lifespan Cancer Institute at Brown University in Providence, R.I.

“But you can’t avoid noticing how the curves come back together in terms of disease-free survival when your effective treatment is limited to 24 months,” he added.

An apparent risk of late brain recurrence in the gefitinib arm is also a concern, Dr. Azzoli said. “So ... longer duration of treatment with a drug that has better control of CNS [central nervous system] disease, such as osimertinib, may improve both DFS and OS,” he added.

Only about 50% of patients in the chemotherapy arm received a TKI at recurrence. The post hoc analysis showing that TKI recipients had the best outcomes raises the question of whether “the survival benefit could be conferred by delivering a superior drug merely at recurrence, or is there benefit to earlier delivery of an effective drug,” Dr. Azzoli said.

Given the high cost of continuous therapy, biomarker refinement could help improve treatment decision-making, he said, noting that “early testing of blood DNA to detect cancer in the body as minimal residual disease is showing promise,” and that many phase 3 studies of EGFR-TKIs are ongoing.

The current trial was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu disclosed relationships with AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/China, Lilly, MSD Oncology, Pfizer, and Roche. Dr. Azzoli reported having no disclosures.

sworcester@mdedge.com

SOURCE: Wu Y et al. ASCO 2020, Abstract 9005.

Adjuvant gefitinib provides no overall survival (OS) benefit over standard chemotherapy for EGFR-mutant, resected, stage II-IIIA non–small cell lung cancer (NSCLC), according to final results from the phase 3 ADJUVANT trial.

The median OS was 75.5 months in patients randomized to adjuvant gefitinib and 62.8 months in patients randomized to vinorelbine plus cisplatin.

Yi-Long Wu, MD, of Guangdong Lung Cancer Institute in Guangzhou, China, reported these results as part of the American Society of Clinical Oncology virtual scientific program.

Prior results from this trial had shown a disease-free survival (DFS) benefit with gefitinib, but this did not translate to an OS benefit at the final analysis, Dr. Wu said.

He noted, however, that the median OS of 75.5 months in the gefitinib arm “was one of the best in resected EGFR-mutant non–small cell lung cancer, compared with historical data.”

The findings also suggest a possible benefit with at least 18 months of gefitinib and show that adjuvant EGFR tyrosine kinase inhibitors (TKIs) should be considered the optimal therapy to improve DFS and achieve potentially better OS in this setting, Dr. Wu said.
 

Study details and DFS

The ADJUVANT trial (NCT01405079) randomized 222 patients, aged 18-75 years, with EGFR-mutant, stage II-IIIA (N1-N2) NSCLC who had undergone complete resection. Patients were enrolled at 27 sites between September 2011 and April 2014.

The patients were randomized 1:1 to receive 250 mg of gefitinib once daily for 24 months, or 25 mg/m² of vinorelbine on days 1 and 8 plus 75 mg/m² of cisplatin on day 1 every 3 weeks for 4 cycles.

The intent-to-treat (ITT) population included 111 patients in each arm. The per-protocol population included 106 patients in the gefitinib arm and 87 patients in the chemotherapy arm.

Primary results from this trial showed a significant improvement in DFS with gefitinib (Lancet Oncol. 2018 Jan;19[1]:139-48). That improvement was maintained in the final analysis.

The median DFS was 30.8 months in the gefitinib arm and 19.8 months in the chemotherapy arm for both the ITT and per-protocol populations. The hazard ratio (HR) was 0.56 (P = .001) in the ITT population and 0.51 (P < .001) in the per-protocol population.

In the ITT population, the 5-year DFS rates were 22.6% in the gefitinib arm and 23.2% in the chemotherapy arm. In the per-protocol population, the 5-year DFS rates were 22.6% and 22.8%, respectively.

OS results

The median OS was 75.5 months in the gefitinib arm and 62.8 months in the chemotherapy arm for both the ITT and per-protocol populations. The HR was 0.92 in both the ITT (P = .674) and per-protocol populations (P = .686).

In the ITT population, the 5-year OS rates were 53.2% in the gefitinib arm and 51.2% in the chemotherapy arm. In the per-protocol population, the 5-year OS rates were 53.2% and 50.7%, respectively.

Subgroup analyses by age, gender, lymph node status, and EGFR mutation showed trends toward improved OS with gefitinib, but the differences were not statistically significant.

The researchers conducted a post hoc analysis to assess the effect of subsequent treatment on patient outcomes. The analysis showed that patients who received gefitinib with subsequent EGFR-TKIs had the best responses and OS.

The median OS was not reached among patients who received gefitinib and subsequent EGFR-TKIs, whereas the median OS ranged from 15.6 months to 62.8 months in other groups. The shortest OS was observed in patients who received adjuvant chemotherapy without subsequent therapy.

The duration of gefitinib treatment also appeared to affect OS. The median OS was 35.7 months in patients who received gefitinib for less than 18 months, and the median OS was not reached in patients who received gefitinib for 18 months or longer (HR, 0.38; P < .001).
 

Implications and potential next steps

Despite the lack of OS improvement with gefitinib, “all of the patients on this study did much, much better than historical non–small cell lung cancer not specified by the EGFR mutation, with 70 months median survival compared to 35 months median survival for N2-positive disease,” said invited discussant Christopher G. Azzoli, MD, director of thoracic oncology at Lifespan Cancer Institute at Brown University in Providence, R.I.

“But you can’t avoid noticing how the curves come back together in terms of disease-free survival when your effective treatment is limited to 24 months,” he added.

An apparent risk of late brain recurrence in the gefitinib arm is also a concern, Dr. Azzoli said. “So ... longer duration of treatment with a drug that has better control of CNS [central nervous system] disease, such as osimertinib, may improve both DFS and OS,” he added.

Only about 50% of patients in the chemotherapy arm received a TKI at recurrence. The post hoc analysis showing that TKI recipients had the best outcomes raises the question of whether “the survival benefit could be conferred by delivering a superior drug merely at recurrence, or is there benefit to earlier delivery of an effective drug,” Dr. Azzoli said.

Given the high cost of continuous therapy, biomarker refinement could help improve treatment decision-making, he said, noting that “early testing of blood DNA to detect cancer in the body as minimal residual disease is showing promise,” and that many phase 3 studies of EGFR-TKIs are ongoing.

The current trial was sponsored by the Guangdong Association of Clinical Trials. Dr. Wu disclosed relationships with AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb/China, Lilly, MSD Oncology, Pfizer, and Roche. Dr. Azzoli reported having no disclosures.

sworcester@mdedge.com

SOURCE: Wu Y et al. ASCO 2020, Abstract 9005.

The MET inhibitor tepotinib produced responses in about half of advanced non–small cell lung cancer (NSCLC) patients with confirmed MET exon 14–skipping mutations in an open-label, phase 2 study.

The objective response rate was 46.5% among the 99 patients followed for 9 or more months, as assessed by independent reviewers. There were no complete responders, according to the reviewers.

However, the response rate according to investigator assessment was 55.6%, including two responses that were judged to be complete.

The median duration of response was 11.1 months according to reviewers and 14 months according to investigators.

“The success of this trial, alongside other studies on the same class of drugs, establishes MET exon 14 as an actionable target for non–small cell lung cancer,” said senior author Xiuning Le, MD, PhD, assistant professor in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Le presented results from this trial as part of the American Society of Clinical Oncology virtual scientific program. Results were published simultaneously in the New England Journal of Medicine.

The trial, dubbed VISION, already won tepotinib approval in Japan to treat NSCLC patients with MET exon 14–skipping mutations. The Food and Drug Administration has granted tepotinib breakthrough status, and Merck, the drug’s manufacturer, plans to submit tepotinib for review this year.

The VISION trial enrolled 152 patients with NSCLC – 99 with at least 9 months of follow-up and 53 with shorter follow-up. The patients’ MET exon 14 mutations were confirmed by liquid or tissue biopsy.

The patients’ median age at baseline was 74 years, 54% were men, and almost half had no smoking history. Patients received tepotinib at 500 mg daily until disease progression or intolerable toxicity.

Overall, the VISION results “compare favorably” with those from studies of other MET inhibitors, the investigators wrote.

The 46.5% objective response rate (per independent reviewers) included the 99 patients with follow-up of at least 9 months who were liquid- or tissue-biopsy positive (combined group). The response rate was 48.5% among the 66 patients with positive liquid biopsies and 50% among the 60 patients with positive tissue biopsies.

The median progression-free survival was 8.5 months in the combined group, 8.5 months in the liquid-biopsy group, and 11 months in the tissue-biopsy group. The median overall survival was 17.1 months, 15.8 months, and 22.3 months, respectively.

The 11 patients with brain metastases at baseline had results that were in line with the other patients’ results. Patients with brain metastases had an objective response rate of 54.5%, a median response duration of 9.5 months, and a median progression-free survival of 10.9 months.

Overall, 88.8% of patients reported adverse events related to treatment, including peripheral edema in 63.2%, nausea in 25.7%, and diarrhea in 21.7%.

Grade 3-4 adverse events occurred in 27% of patients. Peripheral edema was the most common of these events, reported in 7.2% of patients.

“Proactive monitoring for peripheral edema is recommended and can be managed with temporary discontinuation of tepotinib or dose reduction,” the investigators wrote.

The death of a 79-year-old patient with respiratory failure and dyspnea, secondary to interstitial lung disease, was the only death considered to be treatment related.

The study was funded by Merck. Dr. Le and other investigators disclosed relationships, including employment, with the company.

aotto@mdedge.com

SOURCE: Le X et al. ASCO 2020, Abstract 9556.

The MET inhibitor tepotinib produced responses in about half of advanced non–small cell lung cancer (NSCLC) patients with confirmed MET exon 14–skipping mutations in an open-label, phase 2 study.

The objective response rate was 46.5% among the 99 patients followed for 9 or more months, as assessed by independent reviewers. There were no complete responders, according to the reviewers.

However, the response rate according to investigator assessment was 55.6%, including two responses that were judged to be complete.

The median duration of response was 11.1 months according to reviewers and 14 months according to investigators.

“The success of this trial, alongside other studies on the same class of drugs, establishes MET exon 14 as an actionable target for non–small cell lung cancer,” said senior author Xiuning Le, MD, PhD, assistant professor in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Le presented results from this trial as part of the American Society of Clinical Oncology virtual scientific program. Results were published simultaneously in the New England Journal of Medicine.

The trial, dubbed VISION, already won tepotinib approval in Japan to treat NSCLC patients with MET exon 14–skipping mutations. The Food and Drug Administration has granted tepotinib breakthrough status, and Merck, the drug’s manufacturer, plans to submit tepotinib for review this year.

The VISION trial enrolled 152 patients with NSCLC – 99 with at least 9 months of follow-up and 53 with shorter follow-up. The patients’ MET exon 14 mutations were confirmed by liquid or tissue biopsy.

The patients’ median age at baseline was 74 years, 54% were men, and almost half had no smoking history. Patients received tepotinib at 500 mg daily until disease progression or intolerable toxicity.

Overall, the VISION results “compare favorably” with those from studies of other MET inhibitors, the investigators wrote.

The 46.5% objective response rate (per independent reviewers) included the 99 patients with follow-up of at least 9 months who were liquid- or tissue-biopsy positive (combined group). The response rate was 48.5% among the 66 patients with positive liquid biopsies and 50% among the 60 patients with positive tissue biopsies.

The median progression-free survival was 8.5 months in the combined group, 8.5 months in the liquid-biopsy group, and 11 months in the tissue-biopsy group. The median overall survival was 17.1 months, 15.8 months, and 22.3 months, respectively.

The 11 patients with brain metastases at baseline had results that were in line with the other patients’ results. Patients with brain metastases had an objective response rate of 54.5%, a median response duration of 9.5 months, and a median progression-free survival of 10.9 months.

Overall, 88.8% of patients reported adverse events related to treatment, including peripheral edema in 63.2%, nausea in 25.7%, and diarrhea in 21.7%.

Grade 3-4 adverse events occurred in 27% of patients. Peripheral edema was the most common of these events, reported in 7.2% of patients.

“Proactive monitoring for peripheral edema is recommended and can be managed with temporary discontinuation of tepotinib or dose reduction,” the investigators wrote.

The death of a 79-year-old patient with respiratory failure and dyspnea, secondary to interstitial lung disease, was the only death considered to be treatment related.

The study was funded by Merck. Dr. Le and other investigators disclosed relationships, including employment, with the company.

aotto@mdedge.com

SOURCE: Le X et al. ASCO 2020, Abstract 9556.

The MET inhibitor tepotinib produced responses in about half of advanced non–small cell lung cancer (NSCLC) patients with confirmed MET exon 14–skipping mutations in an open-label, phase 2 study.

The objective response rate was 46.5% among the 99 patients followed for 9 or more months, as assessed by independent reviewers. There were no complete responders, according to the reviewers.

However, the response rate according to investigator assessment was 55.6%, including two responses that were judged to be complete.

The median duration of response was 11.1 months according to reviewers and 14 months according to investigators.

“The success of this trial, alongside other studies on the same class of drugs, establishes MET exon 14 as an actionable target for non–small cell lung cancer,” said senior author Xiuning Le, MD, PhD, assistant professor in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston.

Dr. Le presented results from this trial as part of the American Society of Clinical Oncology virtual scientific program. Results were published simultaneously in the New England Journal of Medicine.

The trial, dubbed VISION, already won tepotinib approval in Japan to treat NSCLC patients with MET exon 14–skipping mutations. The Food and Drug Administration has granted tepotinib breakthrough status, and Merck, the drug’s manufacturer, plans to submit tepotinib for review this year.

The VISION trial enrolled 152 patients with NSCLC – 99 with at least 9 months of follow-up and 53 with shorter follow-up. The patients’ MET exon 14 mutations were confirmed by liquid or tissue biopsy.

The patients’ median age at baseline was 74 years, 54% were men, and almost half had no smoking history. Patients received tepotinib at 500 mg daily until disease progression or intolerable toxicity.

Overall, the VISION results “compare favorably” with those from studies of other MET inhibitors, the investigators wrote.

The 46.5% objective response rate (per independent reviewers) included the 99 patients with follow-up of at least 9 months who were liquid- or tissue-biopsy positive (combined group). The response rate was 48.5% among the 66 patients with positive liquid biopsies and 50% among the 60 patients with positive tissue biopsies.

The median progression-free survival was 8.5 months in the combined group, 8.5 months in the liquid-biopsy group, and 11 months in the tissue-biopsy group. The median overall survival was 17.1 months, 15.8 months, and 22.3 months, respectively.

The 11 patients with brain metastases at baseline had results that were in line with the other patients’ results. Patients with brain metastases had an objective response rate of 54.5%, a median response duration of 9.5 months, and a median progression-free survival of 10.9 months.

Overall, 88.8% of patients reported adverse events related to treatment, including peripheral edema in 63.2%, nausea in 25.7%, and diarrhea in 21.7%.

Grade 3-4 adverse events occurred in 27% of patients. Peripheral edema was the most common of these events, reported in 7.2% of patients.

“Proactive monitoring for peripheral edema is recommended and can be managed with temporary discontinuation of tepotinib or dose reduction,” the investigators wrote.

The death of a 79-year-old patient with respiratory failure and dyspnea, secondary to interstitial lung disease, was the only death considered to be treatment related.

The study was funded by Merck. Dr. Le and other investigators disclosed relationships, including employment, with the company.

aotto@mdedge.com

SOURCE: Le X et al. ASCO 2020, Abstract 9556.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Approximately one-fifth of patients undergoing hematopoietic stem cell transplantation (HSCT) develop posttraumatic stress disorder (PTSD), based on a retrospective analysis.

Patient factors at time of transplantation, such as low quality of life and high anxiety, predicted PTSD 6 months later, reported lead author Sarah Griffith, MD, of Massachusetts General Hospital, Boston, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“We know that patients admitted for HSCT are often isolated in the hospital for a prolonged period of time, usually about 3-4 weeks, and that they endure substantial toxicities that impact both their physical and psychological well-being,” Dr. Griffith said. “We also know from the literature that HSCT can be considered a traumatic event and that it may lead to clinically significant PTSD symptoms.” But studies evaluating the prevalence and characteristics of PTSD in this patient population have been lacking, she noted.

Dr. Griffith and her colleagues therefore conducted a retrospective analysis involving 250 adults with hematologic malignancies who underwent autologous or allogeneic HSCT during clinical trials conducted from 2014 to 2016. Median patient age was 56 years.

The first objective of the study was to measure the prevalence of PTSD. The second was to characterize features of PTSD such as intrusion, which entails reliving experiences in the form of nightmares or flashbacks, and hypervigilance, which encompasses insomnia, irritability, and hyperarousal for threat. The third objective was to determine risk factors at baseline.

At time of admission for HSCT, after 2 weeks of hospitalization, and again 6 months after transplantation, patients were evaluated using the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT), and the Hospital Anxiety and Depression Scale (HADS), which measured of quality of life, anxiety, and depression. Six months after HSCT, patients also underwent screening for PTSD with the Post-Traumatic Stress Checklist (PTSD-CL). Multivariate regression models were used to determine predictive risk factors.

Six months after HSCT, 18.9% of patients had clinically significant PTSD symptoms; most common were symptoms of avoidance (92.3%), hypervigilance (92.3%), and intrusion (76.9%). Among those who did not have clinically significant PTSD, almost one-quarter (24.5%) demonstrated significant hypervigilance, while 13.7% showed symptoms of avoidance.

“Clinically significant PTSD symptoms are common in the transplant population,” Dr. Griffith said.

Baseline predictors of PTSD included single status and lower quality of life. More severe PTSD was predicted by single status, younger age, higher baseline scores for anxiety or depression, and increased anxiety during hospitalization.

Concluding her presentation, Dr. Griffith said that the findings, while correlative and not causative, should prompt concern and intervention.

“It is very important to be aware of and to manage PTSD symptoms in these patients,” she said. “There are several baseline factors that can be identified prior to HSCT that may illuminate patients at risk for developing worse PTSD symptoms down the road, and these patients may benefit from tailored supportive care interventions.”

Specifically, Dr. Griffith recommended integrating palliative care into hospitalization, as this has been shown to reduce anxiety.

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., highlighted the importance of the findings, while also noting that the impact of palliative care on risk of PTSD has yet to be demonstrated.

Dr. Shah suggested that future research may be improved through use of a formal diagnosis for PTSD, instead of a PTSD checklist, as was used in the present study.

“And certainly long-term follow-up would be important to evaluate the utility of this tool looking at symptoms beyond 6 months,” she said.

Dr. Shah went on to discuss the relevance of the findings for pediatric populations, as children may face unique risk factors and consequences related to PTSD.

“[PTSD in children] may be impacted by family dynamics and structure,” Dr. Shah said. “Children may also have significant neurocognitive implications as a result of their underlying disease or prior therapy. They may experience chronic pain as they go out into adulthood and long-term survivorship, and may also struggle with symptoms of anxiety and depression.”

According to Dr. Shah, one previous study involving more than 6,000 adult survivors of childhood cancer found that PTSD was relatively common, with prevalence rate of 9%, suggesting that interventional work is necessary.

“Applying the data in the study from Griffith et al. suggests that evaluation in the more proximal posttransplant period for children is needed to specifically evaluate PTSD and symptoms thereof, and to try to use this to identify an opportunity for intervention,” Dr. Shah said.

“Pediatric-specific assessments are essential to optimally capture disease and/or age-specific considerations,” she added.

The study was funded by the Lymphoma and Leukemia Society. The investigators disclosed additional relationships with Vector Oncology, Pfizer, AstraZeneca, and Gaido Health/BCG Digital Ventures.

SOURCE: Griffith et al. ASCO 2020. Abstract # 7505.

Continuing adjuvant imatinib (Gleevec, Novartis) for 3 years rather than stopping at 1 year in patients with high-risk gastrointestinal stromal tumors (GIST) could halve the death rate over 10 years, phase 3 trial data suggest.

The most recent analysis of the SSGXVIII/AIO trial shows that, in about 400 patients who underwent surgery and had a high estimated risk of recurrence, there was a 50% increase in overall survival with longer treatment at 10 years on an efficacy analysis.

Moreover, there was a 30% improvement in recurrence-free survival (RFS) with 3 years vs 1 year of imatinib, with an even greater benefit seen in patients with a common tumor mutation.

The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 11503), held virtually because of the coronavirus pandemic.

Lead author Peter Reichardt, MD, Helios Klinikum Berlin-Buch, Berlin, Germany, said the results show that “3 years of adjuvant imatinib is highly superior” in terms of RFS and overall survival to 1 year of treatment.

“Overall, approximately 50% of deaths can be avoided during the first 10 years of follow-up after surgery with the longer adjuvant imatinib treatment.”

Study discussant Giovanni Grignani, MD, Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy, said that the “burning question” in the sarcoma space is: “Can we improve overall survival by reducing the risk of relapse with a perioperative treatment?

“We would like to able to identify patients for whom the cost of toxicity is paid off by an improvement in their outcome,” he added, noting that this is not achievable “and this is why perioperative treatment is so controversial in oncology.”

Grignani said the picture is a little different for GIST, as the relapse risk is unevenly distributed, the activity of imatinib is “extraordinary,” and the drug toxicity is “certainly bearable but not negligible.”

RFS is, however, affected by the inability of imatinib to eradicate resistant clones left behind by surgery, and replication resumes once the drug is stopped.

The current study nevertheless shows that overall survival “clearly favors 3-year imatinib therapy…with an impressive median follow-up of 119 months [10 years],” commented Patrick Leavey, MD, University of Texas Southwestern Medical Center, Dallas, in a highlights session.

He added that, in GIST, what might be considered “new progress” with the findings “is clarity over the length of imatinib therapy, which ... seems to be safe.”

Reichardt began by noting that several large randomized trials over the past decade have shown that adjuvant imatinib improves both RFS and overall survival.

However, “it is unknown whether imatinib improves overall survival after extended follow-up,” in addition to which “little is known about the long-term safety” of the drug in this setting.

To offer further insights, the protocol of SSGXVIII/AIO was amended in April 2017 to allow for a third analysis to be carried out once the last patient who entered the trial has been followed up for 10 years.
 

More Details

Reichardt recalled that the study, which was an open-label, multicenter phase 3 trial, involved GIST patients who were randomly assigned following surgery in a 1:1 fashion to imatinib for either 12 months or 36 months.

The patients were required to have a high-risk of recurrence, defined as at least one of the following:

• Tumor size >10 cm
• Tumor mitosis count >10/50 on high-powered microscopy (HPF)
• Tumor size >5 cm and mitosis count >5/50 HPF
• Tumor rupture, either spontaneously or at surgery.

Four hundred patients were recruited between February 2004 and September 2008, and 181 patients who were randomly assigned to 12 months of imatinib and 177 to 36 months were included in the efficacy analysis.

The median age of the patients was approximately 61 years, and half were female. The treatment groups were well-balanced in terms of their baseline characteristics.

Of note, 69% of patients in the 1-year treatment group and 71% of those given imatinib for 3 years had a detectable mutation in the KIT exon 11 site. The mean mitosis count was 10/50 and 8/50, respectively.

Over a median follow-up of 119 months (9 years, 11 months), 53% of 1-year treatment patients experienced a recurrence event, and 30% died, of whom 82% died with metastatic GIST.

In the 3-year treatment group, 44% experienced a recurrence event, and 18% died, with 83% of deaths from metastatic GIST.

On intention-to-treat analysis, RFS at 10 years was significantly higher with 3 years of imatinib than with 1 year, at 53% vs 42% (hazard ratio [HR], 0.66; P = .003).

Overall survival at 10 years was also higher with longer imatinib treatment, at 79% with 3 years of therapy vs 65% with 1 year (HR, 0.55; P = .004).

The team found on subgroup analysis that RFS was significantly better with 3-year than 1-year imatinib in patients with:

• A local mitotic count >10 (HR = 0.42)
• A central mitotic count >10 (HR = 0.50)
• A KIT exon 11 tumor mutation (HR = 0.57).

On the efficacy analysis, which included patients who signed informed consent, had GIST at pathology review, and no overt metastases at study entry, the HR for RFS with 3-year vs 1-year therapy was 0.70, whereas the HR for overall survival was 0.50.

Patients treated with imatinib for 3 years had a higher rate of any new cancer during follow-up, at 17%, vs 12% for those treated with imatinib for 1 year. Prostate cancer was the most common form of the disease in both groups.

Cardiac events were, in contrast, evenly distributed between the two groups, with 5% of 3-year patients and 6% of 1-year patients experiencing an event.

The study was funded by Novartis.

Reichardt reports honoraria from Amgen, Bayer, Lilly, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, Clinigen Group, Decipher, Lilly, Novartis, Pfizer, PharmaMar, and Roche; and receiving research funding from Novartis (Inst). Other authors report potential conflicts of interest.

Grignani reports honoraria from Bayer, EISAI, Lilly, Merck Serono, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, EISAI, and PharmaMar; receiving research funding from PharmaMar (Inst); and travel, accommodations, expenses from PharmaMar and Tesaro.

Leavey reports receiving research funding from Elison Pharmaceuticals (Inst).
 

This article first appeared on Medscape.com.

Continuing adjuvant imatinib (Gleevec, Novartis) for 3 years rather than stopping at 1 year in patients with high-risk gastrointestinal stromal tumors (GIST) could halve the death rate over 10 years, phase 3 trial data suggest.

The most recent analysis of the SSGXVIII/AIO trial shows that, in about 400 patients who underwent surgery and had a high estimated risk of recurrence, there was a 50% increase in overall survival with longer treatment at 10 years on an efficacy analysis.

Moreover, there was a 30% improvement in recurrence-free survival (RFS) with 3 years vs 1 year of imatinib, with an even greater benefit seen in patients with a common tumor mutation.

The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 11503), held virtually because of the coronavirus pandemic.

Lead author Peter Reichardt, MD, Helios Klinikum Berlin-Buch, Berlin, Germany, said the results show that “3 years of adjuvant imatinib is highly superior” in terms of RFS and overall survival to 1 year of treatment.

“Overall, approximately 50% of deaths can be avoided during the first 10 years of follow-up after surgery with the longer adjuvant imatinib treatment.”

Study discussant Giovanni Grignani, MD, Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy, said that the “burning question” in the sarcoma space is: “Can we improve overall survival by reducing the risk of relapse with a perioperative treatment?

“We would like to able to identify patients for whom the cost of toxicity is paid off by an improvement in their outcome,” he added, noting that this is not achievable “and this is why perioperative treatment is so controversial in oncology.”

Grignani said the picture is a little different for GIST, as the relapse risk is unevenly distributed, the activity of imatinib is “extraordinary,” and the drug toxicity is “certainly bearable but not negligible.”

RFS is, however, affected by the inability of imatinib to eradicate resistant clones left behind by surgery, and replication resumes once the drug is stopped.

The current study nevertheless shows that overall survival “clearly favors 3-year imatinib therapy…with an impressive median follow-up of 119 months [10 years],” commented Patrick Leavey, MD, University of Texas Southwestern Medical Center, Dallas, in a highlights session.

He added that, in GIST, what might be considered “new progress” with the findings “is clarity over the length of imatinib therapy, which ... seems to be safe.”

Reichardt began by noting that several large randomized trials over the past decade have shown that adjuvant imatinib improves both RFS and overall survival.

However, “it is unknown whether imatinib improves overall survival after extended follow-up,” in addition to which “little is known about the long-term safety” of the drug in this setting.

To offer further insights, the protocol of SSGXVIII/AIO was amended in April 2017 to allow for a third analysis to be carried out once the last patient who entered the trial has been followed up for 10 years.
 

More Details

Reichardt recalled that the study, which was an open-label, multicenter phase 3 trial, involved GIST patients who were randomly assigned following surgery in a 1:1 fashion to imatinib for either 12 months or 36 months.

The patients were required to have a high-risk of recurrence, defined as at least one of the following:

• Tumor size >10 cm
• Tumor mitosis count >10/50 on high-powered microscopy (HPF)
• Tumor size >5 cm and mitosis count >5/50 HPF
• Tumor rupture, either spontaneously or at surgery.

Four hundred patients were recruited between February 2004 and September 2008, and 181 patients who were randomly assigned to 12 months of imatinib and 177 to 36 months were included in the efficacy analysis.

The median age of the patients was approximately 61 years, and half were female. The treatment groups were well-balanced in terms of their baseline characteristics.

Of note, 69% of patients in the 1-year treatment group and 71% of those given imatinib for 3 years had a detectable mutation in the KIT exon 11 site. The mean mitosis count was 10/50 and 8/50, respectively.

Over a median follow-up of 119 months (9 years, 11 months), 53% of 1-year treatment patients experienced a recurrence event, and 30% died, of whom 82% died with metastatic GIST.

In the 3-year treatment group, 44% experienced a recurrence event, and 18% died, with 83% of deaths from metastatic GIST.

On intention-to-treat analysis, RFS at 10 years was significantly higher with 3 years of imatinib than with 1 year, at 53% vs 42% (hazard ratio [HR], 0.66; P = .003).

Overall survival at 10 years was also higher with longer imatinib treatment, at 79% with 3 years of therapy vs 65% with 1 year (HR, 0.55; P = .004).

The team found on subgroup analysis that RFS was significantly better with 3-year than 1-year imatinib in patients with:

• A local mitotic count >10 (HR = 0.42)
• A central mitotic count >10 (HR = 0.50)
• A KIT exon 11 tumor mutation (HR = 0.57).

On the efficacy analysis, which included patients who signed informed consent, had GIST at pathology review, and no overt metastases at study entry, the HR for RFS with 3-year vs 1-year therapy was 0.70, whereas the HR for overall survival was 0.50.

Patients treated with imatinib for 3 years had a higher rate of any new cancer during follow-up, at 17%, vs 12% for those treated with imatinib for 1 year. Prostate cancer was the most common form of the disease in both groups.

Cardiac events were, in contrast, evenly distributed between the two groups, with 5% of 3-year patients and 6% of 1-year patients experiencing an event.

The study was funded by Novartis.

Reichardt reports honoraria from Amgen, Bayer, Lilly, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, Clinigen Group, Decipher, Lilly, Novartis, Pfizer, PharmaMar, and Roche; and receiving research funding from Novartis (Inst). Other authors report potential conflicts of interest.

Grignani reports honoraria from Bayer, EISAI, Lilly, Merck Serono, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, EISAI, and PharmaMar; receiving research funding from PharmaMar (Inst); and travel, accommodations, expenses from PharmaMar and Tesaro.

Leavey reports receiving research funding from Elison Pharmaceuticals (Inst).
 

This article first appeared on Medscape.com.

Continuing adjuvant imatinib (Gleevec, Novartis) for 3 years rather than stopping at 1 year in patients with high-risk gastrointestinal stromal tumors (GIST) could halve the death rate over 10 years, phase 3 trial data suggest.

The most recent analysis of the SSGXVIII/AIO trial shows that, in about 400 patients who underwent surgery and had a high estimated risk of recurrence, there was a 50% increase in overall survival with longer treatment at 10 years on an efficacy analysis.

Moreover, there was a 30% improvement in recurrence-free survival (RFS) with 3 years vs 1 year of imatinib, with an even greater benefit seen in patients with a common tumor mutation.

The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 11503), held virtually because of the coronavirus pandemic.

Lead author Peter Reichardt, MD, Helios Klinikum Berlin-Buch, Berlin, Germany, said the results show that “3 years of adjuvant imatinib is highly superior” in terms of RFS and overall survival to 1 year of treatment.

“Overall, approximately 50% of deaths can be avoided during the first 10 years of follow-up after surgery with the longer adjuvant imatinib treatment.”

Study discussant Giovanni Grignani, MD, Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy, said that the “burning question” in the sarcoma space is: “Can we improve overall survival by reducing the risk of relapse with a perioperative treatment?

“We would like to able to identify patients for whom the cost of toxicity is paid off by an improvement in their outcome,” he added, noting that this is not achievable “and this is why perioperative treatment is so controversial in oncology.”

Grignani said the picture is a little different for GIST, as the relapse risk is unevenly distributed, the activity of imatinib is “extraordinary,” and the drug toxicity is “certainly bearable but not negligible.”

RFS is, however, affected by the inability of imatinib to eradicate resistant clones left behind by surgery, and replication resumes once the drug is stopped.

The current study nevertheless shows that overall survival “clearly favors 3-year imatinib therapy…with an impressive median follow-up of 119 months [10 years],” commented Patrick Leavey, MD, University of Texas Southwestern Medical Center, Dallas, in a highlights session.

He added that, in GIST, what might be considered “new progress” with the findings “is clarity over the length of imatinib therapy, which ... seems to be safe.”

Reichardt began by noting that several large randomized trials over the past decade have shown that adjuvant imatinib improves both RFS and overall survival.

However, “it is unknown whether imatinib improves overall survival after extended follow-up,” in addition to which “little is known about the long-term safety” of the drug in this setting.

To offer further insights, the protocol of SSGXVIII/AIO was amended in April 2017 to allow for a third analysis to be carried out once the last patient who entered the trial has been followed up for 10 years.
 

More Details

Reichardt recalled that the study, which was an open-label, multicenter phase 3 trial, involved GIST patients who were randomly assigned following surgery in a 1:1 fashion to imatinib for either 12 months or 36 months.

The patients were required to have a high-risk of recurrence, defined as at least one of the following:

• Tumor size >10 cm
• Tumor mitosis count >10/50 on high-powered microscopy (HPF)
• Tumor size >5 cm and mitosis count >5/50 HPF
• Tumor rupture, either spontaneously or at surgery.

Four hundred patients were recruited between February 2004 and September 2008, and 181 patients who were randomly assigned to 12 months of imatinib and 177 to 36 months were included in the efficacy analysis.

The median age of the patients was approximately 61 years, and half were female. The treatment groups were well-balanced in terms of their baseline characteristics.

Of note, 69% of patients in the 1-year treatment group and 71% of those given imatinib for 3 years had a detectable mutation in the KIT exon 11 site. The mean mitosis count was 10/50 and 8/50, respectively.

Over a median follow-up of 119 months (9 years, 11 months), 53% of 1-year treatment patients experienced a recurrence event, and 30% died, of whom 82% died with metastatic GIST.

In the 3-year treatment group, 44% experienced a recurrence event, and 18% died, with 83% of deaths from metastatic GIST.

On intention-to-treat analysis, RFS at 10 years was significantly higher with 3 years of imatinib than with 1 year, at 53% vs 42% (hazard ratio [HR], 0.66; P = .003).

Overall survival at 10 years was also higher with longer imatinib treatment, at 79% with 3 years of therapy vs 65% with 1 year (HR, 0.55; P = .004).

The team found on subgroup analysis that RFS was significantly better with 3-year than 1-year imatinib in patients with:

• A local mitotic count >10 (HR = 0.42)
• A central mitotic count >10 (HR = 0.50)
• A KIT exon 11 tumor mutation (HR = 0.57).

On the efficacy analysis, which included patients who signed informed consent, had GIST at pathology review, and no overt metastases at study entry, the HR for RFS with 3-year vs 1-year therapy was 0.70, whereas the HR for overall survival was 0.50.

Patients treated with imatinib for 3 years had a higher rate of any new cancer during follow-up, at 17%, vs 12% for those treated with imatinib for 1 year. Prostate cancer was the most common form of the disease in both groups.

Cardiac events were, in contrast, evenly distributed between the two groups, with 5% of 3-year patients and 6% of 1-year patients experiencing an event.

The study was funded by Novartis.

Reichardt reports honoraria from Amgen, Bayer, Lilly, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, Clinigen Group, Decipher, Lilly, Novartis, Pfizer, PharmaMar, and Roche; and receiving research funding from Novartis (Inst). Other authors report potential conflicts of interest.

Grignani reports honoraria from Bayer, EISAI, Lilly, Merck Serono, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, EISAI, and PharmaMar; receiving research funding from PharmaMar (Inst); and travel, accommodations, expenses from PharmaMar and Tesaro.

Leavey reports receiving research funding from Elison Pharmaceuticals (Inst).
 

This article first appeared on Medscape.com.

Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.

Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.

At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.

The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).

There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
 

‘Compelling’ data with caveats

The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.

“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”

The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.

However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.

Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.

Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
 

Additional details

The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.

The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.

Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.

One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.

Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.

The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).

The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.

aotto@mdedge.com

SOURCE: Wang X et al. ASCO 2020, Abstract 9508.

Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.

Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.

At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.

The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).

There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
 

‘Compelling’ data with caveats

The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.

“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”

The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.

However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.

Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.

Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
 

Additional details

The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.

The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.

Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.

One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.

Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.

The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).

The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.

aotto@mdedge.com

SOURCE: Wang X et al. ASCO 2020, Abstract 9508.

Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.

Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.

At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.

The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).

There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
 

‘Compelling’ data with caveats

The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.

“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”

The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.

However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.

Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.

Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
 

Additional details

The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.

The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.

Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.

One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.

Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.

The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).

The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.

aotto@mdedge.com

SOURCE: Wang X et al. ASCO 2020, Abstract 9508.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

Adding the immune checkpoint inhibitor pembrolizumab to chemotherapy resulted in a modest improvement in progression-free survival (PFS) but no overall survival (OS) benefit as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC), results of the KEYNOTE-604 study showed.

Among 453 patients with ES-SCLC randomized to receive pembrolizumab plus etoposide and a platinum agent (EP) or placebo, the median PFS was 4.5 months with pembrolizumab and with 4.3 months with placebo.

This difference, although small, met the prespecified definition for significance, with a hazard ratio favoring pembrolizumab of 0.75 (P = .0023), reported Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Median OS, the other primary endpoint, was 10.8 months for patients who received pembrolizumab and 9.7 months for those who received placebo. Although this translated to a hazard ratio of 0.80 for pembrolizumab, the P value of .0164 missed the prespecified threshold of .0128 and was therefore not statistically significant.

Dr. Rudin presented these results as part of the American Society of Clinical Oncology virtual scientific program. The study was also published online to coincide with the abstract’s release in the Journal of Clinical Oncology.
 

Beneficial but not practice-changing (yet)

“The addition of pembrolizumab results in durable responses in a subset of patients,” Dr. Rudin said. “I believe additional correlative analyses may help to identify those patients who derive long-term benefit from pembrolizumab.

“The safety profile was manageable with no new or unexpected toxicities. Taken together, these data support the benefit of pembrolizumab in patients with small cell lung cancer and add to the growing body of evidence supporting the value of immune checkpoint inhibitors in a historically difficult-to-treat cancer.”

The results suggest combination pembrolizumab and chemotherapy offers a “viable platform for a novel treatment strategy,” said invited discussant Taofeek K. Owonikoko, MD, PhD, director of thoracic oncology at the Winship Cancer Institute of Emory University in Atlanta.

However, because the trial did not meet the predefined threshold for success, “the immediate impact on practice of this trial is limited at present, and any future impact will have to be supported by regulatory decision,” Dr. Owonikoko said.

“The outcome of this trial also highlights the need for an uncomplicated study design and straightforward analytical plan to ensure accurate results,” he added.
 

Study details

KEYNOTE-604 investigators enrolled 453 patients with ES-SCLC who had no prior systemic therapy, good performance status, and a life expectancy of at least 3 months. Patients were stratified by type of platinum agent (cisplatin vs. carboplatin), Eastern Cooperative Oncology Group performance status 0 or 1, and lactate dehydrogenase levels below or above the upper limit of normal.

Patients were randomized to receive pembrolizumab at 200 mg or normal saline placebo on day 1. Both arms also received etoposide at 100 mg/m² on days 1-3 and investigator’s choice of carboplatin to an area under the curve of 5 on day 1 or cisplatin at 75 mg/m² on day 1 for four cycles every 3 weeks.

The assigned agent (pembrolizumab or placebo) could then be continued as maintenance therapy for up to 31 cycles every 21 days.

Patients with a complete or partial response after cycle 4 could receive up to 25 Gy of prophylactic cranial irradiation delivered over 10 fractions at the investigator’s discretion.
 

Survival and response

As noted, the median PFS was modestly but significantly longer with pembrolizumab plus EP at the second interim analysis, the protocol-specified time for final PFS analysis. The estimated 12-months PFS rates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP.

The final analysis was planned to occur about 31 months after the start of the study or when 284 deaths had occurred, whichever was later. At the final analysis, the median PFS was 4.8 months in the pembrolizumab arm and 4.3 months in the placebo arm. The hazard ratio was 0.73 (95% confidence interval 0.60-0.88).

The 12-month OS rate was 45.1% in the pembrolizumab arm and 39.6% in the placebo arm. Respective 24-month OS rates were 22.5% and 11.2%.

Overall responses rates were 70.6% in the pembrolizumab arm and 61.8% in the placebo arm. There were four and two complete responses per arm, respectively.
 

Safety

Approximately 75% of patients in both arms experienced grade 3 or 4 adverse events.

Fatal adverse events occurred in 6.3% of patients in the pembrolizumab arm and 5.4% in the control arm. The rates of death attributed to study treatment were identical, at 2.7% in each arm.

Events leading to discontinuation occurred in 14.8% of patients who received pembrolizumab and 6.3% of patients who received placebo. Adverse events leading to all treatment discontinuation were similar, at 4% and 3.6%, respectively.

The most common adverse events were hematologic, which are common with EP chemotherapy and did not appear to be exacerbated by the addition of pembrolizumab. Aside from hematologic toxicities, most events were of grade 1 or 2 severity.

Immune-mediated adverse events of any kind occurred in 24.7% of patients in the pembrolizumab arm and 10.3% of those in the placebo arm. Grade 3 or 4 immune-mediated events occurred in 7.2% and 1.3%, respectively.

There were no deaths from immune-mediated reactions in the pembrolizumab arm, but one patient on placebo died from pneumonia.

Merck Sharp & Dohme supported the study. Dr. Rudin disclosed institutional research funding from Merck and a consulting or advisory role for other companies. Dr. Owonikoko disclosed a consulting/advisory role and institutional research funding from Merck and others, and he is a cofounder and stock owner in Cambium Oncology.

SOURCE: Rudin CM et al. ASCO 2020. Abstract 9001.

Adding the immune checkpoint inhibitor pembrolizumab to chemotherapy resulted in a modest improvement in progression-free survival (PFS) but no overall survival (OS) benefit as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC), results of the KEYNOTE-604 study showed.

Among 453 patients with ES-SCLC randomized to receive pembrolizumab plus etoposide and a platinum agent (EP) or placebo, the median PFS was 4.5 months with pembrolizumab and with 4.3 months with placebo.

This difference, although small, met the prespecified definition for significance, with a hazard ratio favoring pembrolizumab of 0.75 (P = .0023), reported Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Median OS, the other primary endpoint, was 10.8 months for patients who received pembrolizumab and 9.7 months for those who received placebo. Although this translated to a hazard ratio of 0.80 for pembrolizumab, the P value of .0164 missed the prespecified threshold of .0128 and was therefore not statistically significant.

Dr. Rudin presented these results as part of the American Society of Clinical Oncology virtual scientific program. The study was also published online to coincide with the abstract’s release in the Journal of Clinical Oncology.
 

Beneficial but not practice-changing (yet)

“The addition of pembrolizumab results in durable responses in a subset of patients,” Dr. Rudin said. “I believe additional correlative analyses may help to identify those patients who derive long-term benefit from pembrolizumab.

“The safety profile was manageable with no new or unexpected toxicities. Taken together, these data support the benefit of pembrolizumab in patients with small cell lung cancer and add to the growing body of evidence supporting the value of immune checkpoint inhibitors in a historically difficult-to-treat cancer.”

The results suggest combination pembrolizumab and chemotherapy offers a “viable platform for a novel treatment strategy,” said invited discussant Taofeek K. Owonikoko, MD, PhD, director of thoracic oncology at the Winship Cancer Institute of Emory University in Atlanta.

However, because the trial did not meet the predefined threshold for success, “the immediate impact on practice of this trial is limited at present, and any future impact will have to be supported by regulatory decision,” Dr. Owonikoko said.

“The outcome of this trial also highlights the need for an uncomplicated study design and straightforward analytical plan to ensure accurate results,” he added.
 

Study details

KEYNOTE-604 investigators enrolled 453 patients with ES-SCLC who had no prior systemic therapy, good performance status, and a life expectancy of at least 3 months. Patients were stratified by type of platinum agent (cisplatin vs. carboplatin), Eastern Cooperative Oncology Group performance status 0 or 1, and lactate dehydrogenase levels below or above the upper limit of normal.

Patients were randomized to receive pembrolizumab at 200 mg or normal saline placebo on day 1. Both arms also received etoposide at 100 mg/m² on days 1-3 and investigator’s choice of carboplatin to an area under the curve of 5 on day 1 or cisplatin at 75 mg/m² on day 1 for four cycles every 3 weeks.

The assigned agent (pembrolizumab or placebo) could then be continued as maintenance therapy for up to 31 cycles every 21 days.

Patients with a complete or partial response after cycle 4 could receive up to 25 Gy of prophylactic cranial irradiation delivered over 10 fractions at the investigator’s discretion.
 

Survival and response

As noted, the median PFS was modestly but significantly longer with pembrolizumab plus EP at the second interim analysis, the protocol-specified time for final PFS analysis. The estimated 12-months PFS rates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP.

The final analysis was planned to occur about 31 months after the start of the study or when 284 deaths had occurred, whichever was later. At the final analysis, the median PFS was 4.8 months in the pembrolizumab arm and 4.3 months in the placebo arm. The hazard ratio was 0.73 (95% confidence interval 0.60-0.88).

The 12-month OS rate was 45.1% in the pembrolizumab arm and 39.6% in the placebo arm. Respective 24-month OS rates were 22.5% and 11.2%.

Overall responses rates were 70.6% in the pembrolizumab arm and 61.8% in the placebo arm. There were four and two complete responses per arm, respectively.
 

Safety

Approximately 75% of patients in both arms experienced grade 3 or 4 adverse events.

Fatal adverse events occurred in 6.3% of patients in the pembrolizumab arm and 5.4% in the control arm. The rates of death attributed to study treatment were identical, at 2.7% in each arm.

Events leading to discontinuation occurred in 14.8% of patients who received pembrolizumab and 6.3% of patients who received placebo. Adverse events leading to all treatment discontinuation were similar, at 4% and 3.6%, respectively.

The most common adverse events were hematologic, which are common with EP chemotherapy and did not appear to be exacerbated by the addition of pembrolizumab. Aside from hematologic toxicities, most events were of grade 1 or 2 severity.

Immune-mediated adverse events of any kind occurred in 24.7% of patients in the pembrolizumab arm and 10.3% of those in the placebo arm. Grade 3 or 4 immune-mediated events occurred in 7.2% and 1.3%, respectively.

There were no deaths from immune-mediated reactions in the pembrolizumab arm, but one patient on placebo died from pneumonia.

Merck Sharp & Dohme supported the study. Dr. Rudin disclosed institutional research funding from Merck and a consulting or advisory role for other companies. Dr. Owonikoko disclosed a consulting/advisory role and institutional research funding from Merck and others, and he is a cofounder and stock owner in Cambium Oncology.

SOURCE: Rudin CM et al. ASCO 2020. Abstract 9001.

Adding the immune checkpoint inhibitor pembrolizumab to chemotherapy resulted in a modest improvement in progression-free survival (PFS) but no overall survival (OS) benefit as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC), results of the KEYNOTE-604 study showed.

Among 453 patients with ES-SCLC randomized to receive pembrolizumab plus etoposide and a platinum agent (EP) or placebo, the median PFS was 4.5 months with pembrolizumab and with 4.3 months with placebo.

This difference, although small, met the prespecified definition for significance, with a hazard ratio favoring pembrolizumab of 0.75 (P = .0023), reported Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Median OS, the other primary endpoint, was 10.8 months for patients who received pembrolizumab and 9.7 months for those who received placebo. Although this translated to a hazard ratio of 0.80 for pembrolizumab, the P value of .0164 missed the prespecified threshold of .0128 and was therefore not statistically significant.

Dr. Rudin presented these results as part of the American Society of Clinical Oncology virtual scientific program. The study was also published online to coincide with the abstract’s release in the Journal of Clinical Oncology.
 

Beneficial but not practice-changing (yet)

“The addition of pembrolizumab results in durable responses in a subset of patients,” Dr. Rudin said. “I believe additional correlative analyses may help to identify those patients who derive long-term benefit from pembrolizumab.

“The safety profile was manageable with no new or unexpected toxicities. Taken together, these data support the benefit of pembrolizumab in patients with small cell lung cancer and add to the growing body of evidence supporting the value of immune checkpoint inhibitors in a historically difficult-to-treat cancer.”

The results suggest combination pembrolizumab and chemotherapy offers a “viable platform for a novel treatment strategy,” said invited discussant Taofeek K. Owonikoko, MD, PhD, director of thoracic oncology at the Winship Cancer Institute of Emory University in Atlanta.

However, because the trial did not meet the predefined threshold for success, “the immediate impact on practice of this trial is limited at present, and any future impact will have to be supported by regulatory decision,” Dr. Owonikoko said.

“The outcome of this trial also highlights the need for an uncomplicated study design and straightforward analytical plan to ensure accurate results,” he added.
 

Study details

KEYNOTE-604 investigators enrolled 453 patients with ES-SCLC who had no prior systemic therapy, good performance status, and a life expectancy of at least 3 months. Patients were stratified by type of platinum agent (cisplatin vs. carboplatin), Eastern Cooperative Oncology Group performance status 0 or 1, and lactate dehydrogenase levels below or above the upper limit of normal.

Patients were randomized to receive pembrolizumab at 200 mg or normal saline placebo on day 1. Both arms also received etoposide at 100 mg/m² on days 1-3 and investigator’s choice of carboplatin to an area under the curve of 5 on day 1 or cisplatin at 75 mg/m² on day 1 for four cycles every 3 weeks.

The assigned agent (pembrolizumab or placebo) could then be continued as maintenance therapy for up to 31 cycles every 21 days.

Patients with a complete or partial response after cycle 4 could receive up to 25 Gy of prophylactic cranial irradiation delivered over 10 fractions at the investigator’s discretion.
 

Survival and response

As noted, the median PFS was modestly but significantly longer with pembrolizumab plus EP at the second interim analysis, the protocol-specified time for final PFS analysis. The estimated 12-months PFS rates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP.

The final analysis was planned to occur about 31 months after the start of the study or when 284 deaths had occurred, whichever was later. At the final analysis, the median PFS was 4.8 months in the pembrolizumab arm and 4.3 months in the placebo arm. The hazard ratio was 0.73 (95% confidence interval 0.60-0.88).

The 12-month OS rate was 45.1% in the pembrolizumab arm and 39.6% in the placebo arm. Respective 24-month OS rates were 22.5% and 11.2%.

Overall responses rates were 70.6% in the pembrolizumab arm and 61.8% in the placebo arm. There were four and two complete responses per arm, respectively.
 

Safety

Approximately 75% of patients in both arms experienced grade 3 or 4 adverse events.

Fatal adverse events occurred in 6.3% of patients in the pembrolizumab arm and 5.4% in the control arm. The rates of death attributed to study treatment were identical, at 2.7% in each arm.

Events leading to discontinuation occurred in 14.8% of patients who received pembrolizumab and 6.3% of patients who received placebo. Adverse events leading to all treatment discontinuation were similar, at 4% and 3.6%, respectively.

The most common adverse events were hematologic, which are common with EP chemotherapy and did not appear to be exacerbated by the addition of pembrolizumab. Aside from hematologic toxicities, most events were of grade 1 or 2 severity.

Immune-mediated adverse events of any kind occurred in 24.7% of patients in the pembrolizumab arm and 10.3% of those in the placebo arm. Grade 3 or 4 immune-mediated events occurred in 7.2% and 1.3%, respectively.

There were no deaths from immune-mediated reactions in the pembrolizumab arm, but one patient on placebo died from pneumonia.

Merck Sharp & Dohme supported the study. Dr. Rudin disclosed institutional research funding from Merck and a consulting or advisory role for other companies. Dr. Owonikoko disclosed a consulting/advisory role and institutional research funding from Merck and others, and he is a cofounder and stock owner in Cambium Oncology.

SOURCE: Rudin CM et al. ASCO 2020. Abstract 9001.

CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.

“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.

The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.

Not everyone was as successful.

That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”

Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”

ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.

This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.

Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.

At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”

What did oncologists miss most with virtual ASCO?

Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.

Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.

He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”

The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.

Virtual meeting ‘like homework’

George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).

One of his criticisms struck a nerve – that the online meeting was “like homework.”

“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.

Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.

“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.

Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.

What will happen with ASCO next year?

Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.

“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”

Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”

Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”

Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”

Others were uncertain.

Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”

Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.

“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.

A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.

Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”

Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”

City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
 

“This year was special”

On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.

He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”

Other oncologists praised the accessibility of the virtual meeting.

“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.

“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that  “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”

ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”

With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.

CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.

“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.

The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.

Not everyone was as successful.

That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”

Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”

ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.

This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.

Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.

At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”

What did oncologists miss most with virtual ASCO?

Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.

Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.

He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”

The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.

Virtual meeting ‘like homework’

George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).

One of his criticisms struck a nerve – that the online meeting was “like homework.”

“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.

Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.

“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.

Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.

What will happen with ASCO next year?

Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.

“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”

Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”

Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”

Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”

Others were uncertain.

Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”

Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.

“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.

A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.

Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”

Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”

City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
 

“This year was special”

On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.

He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”

Other oncologists praised the accessibility of the virtual meeting.

“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.

“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that  “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”

ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”

With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.

CYBERSPACE – Hope Rugo, MD, was one of the would-be attendees of the American Society of Clinical Oncology annual meeting who could not access the online event on its first day, Friday, May 29.

“Such a shame – virtual ASCO is nonexistent,” tweeted Rugo, who is from the University of California, San Francisco.

The breast cancer specialist tried for more than hour before finally gaining entry in the late morning.

Not everyone was as successful.

That same day, Arjun Balar, MD, of NYU Langone Health in New York announced on Twitter that he’d quit for the day. “I give up @ASCO. Time for a cocktail.”

Don Dizon, MD, of Brown University in Providence, Rhode Island, tried repeatedly to join the meeting as a live broadcast, using his desktop and laptop computers as well as an iPad. Nothing worked. Limited to seeing data and discussions “after the fact,” Dizon looked to next year, tweeting hopefully: “... fingers crossed for an inperson #ASCO21.”

ASCO did not respond to a request for further information about the technical difficulties of the meeting’s first day.

This year’s meeting, which involved 40,000-plus attendees, was shortened to 3 days and limited to scientific presentations because of the COVID-19 pandemic. Education sessions will be held online August 8-10.

Despite those technical glitches, dozens of virtual meeting attendees praised the online effort, which was assembled in just a few months, and called out virtues such as the quick availability of video transcripts as well as the obvious benefits of low cost, zero travel, and overall convenience. But one sentiment was nearly universal: there’s nothing like the real thing.

At the same time, a Medscape Oncology online meeting poll indicated that nearly half (48%) of the 335 respondents said “no,” they do not envision themselves in person at the real thing in Chicago in 2021. About one fifth (21%) said, “yes, if there is a vaccine.” Roughly 15% said “yes,” and another 15% said “not sure right now.”

What did oncologists miss most with virtual ASCO?

Many said face-to-face (F2F) interactions. Collaboration, networking, and catching up with old friends were some of the stock F2F moments cited as losses.

Others described more idiosyncratic disappointments, including Riyaz Shah, MD, of the Kent Oncology Centre in the UK, who dismissed a future with exclusively virtual meetings.

He tweeted: “Not sustainable. We need to meet F2F. Oncology is an odd one. Exposed to human distress daily (if not hourly). [Very] few people understand what we do, fewer would do it. There aren’t many people we can talk to. I love chewing the cud with my colleagues who are close friends.”

The virtual meeting inspired more social media engagement, but fewer oncologists participated, according to data from social media analytics firm Symplur. This year, 1K users identified as oncologists generated 17.75K tweets. In 2019, 1.3K oncologists put out 15.2K tweets.

Virtual meeting ‘like homework’

George Sledge, MD, of Stanford University, California, asked his 1700 Twitter followers to discuss the virtual ASCO experience, including the spotty functionality of presenter videos (a con) and eating dinner between talks (a pro).

One of his criticisms struck a nerve – that the online meeting was “like homework.”

“ ‘Feels like homework’ is the best expression I [have] read so far!” tweeted Gustavo Gössling, MD, from the Kaplan Oncology Institute in Porto Alegre, Brazil.

Yes, it feels “like studying alone,” agreed Stanford’s Lidia Schapira, MD, in a tweet.

“It’s incredibly boring – let’s bring back F2F next year,” tweeted Ioannis Gounaris, MD, Merck Group, Cambridge, UK, in response to Sledge’s request.

Sledge joined many others in saying that, ultimately, the future should include – and will demand – both virtual and in-person meetings.

What will happen with ASCO next year?

Medscape Medical News asked some virtual attendees whether they envisioned going in person to the ASCO meeting next year in Chicago.

“Counting on it,” said Harold Burstein, MD, PhD, Dana-Farber Cancer Institute, Boston. “But I also recognize that it fully depends on what happens between now and then. Vaccines. Safety of travel. Safety of large, indoor, crowded spaces.”

Despite acknowledging the uncertainty of how things will “play out,” Burstein advised: “Put it on your calendar and make reservations, and make sure the reservations are fully refundable.”

Ahmad Tarhini, MD, from the Moffitt Cancer Center in Tampa, Florida, sounded similarly optimistic: “Hopefully we will have a vaccine by then. I expect the ASCO annual meeting will happen in person in 2021.”

Moffitt colleague Michelle Echevarria Colon, MD, said, “I could see myself attending ... in Chicago in 2021.” And she added: “I think we’ll get to a point where it could happen.”

Others were uncertain.

Ishwaria Subbiah, MD, University of Texas MD Anderson Cancer Center, Houston, said: “If someone told us 6 months ago that our ‘new normal’ would be in this near-total virtual existence, most of us would not have believed them. So it is hard to imagine what our reality will be in a year from now at ASCO 2021.”

Jack West, MD, from City of Hope Comprehensive Cancer Center in Duarte, California, thinks the meeting will be changed for a long time, even if 2021 is a live event.

“While I think that there MIGHT be a live conference, I think it will be many years, if ever, before we see it return to its prior magnitude,” he wrote in an email, echoing remarks previously made by other healthcare professionals about medical meetings in any post–COVID-19 world.

A year from now, said West, “I strongly suspect that we will still be contending with risk of exposure” and that means clinician attendees might, in turn, expose their cancer patients back home.

Despite his wistful “fingers crossed” tweet during ASCO 2020, Brown’s Dizon also recently commented on Medscape that “I wonder whether I will ever sit in a crowded auditorium at an ASCO annual meeting again.”

Sagar Sardesai, MBBS, Ohio State Comprehensive Cancer Center, Columbus, responded: “Unless we have a vaccine that is successful or we can demonstrate enough herd immunity in the United States, I can’t imagine that such large gatherings are a real possibility. We need to protect our vulnerable populations.”

City of Hope’s Cary Presant, MD, acknowledged he is one of those vulnerable people. “In 2021, if the environment is safe for oncologists of my age, I will be in Chicago,” he said. “But with COVID-19 still a threat, I might have to attend only virtually.”
 

“This year was special”

On social media, MD Anderson’s Vivek Subbiah, MD, did not speculate about next year’s meeting but observed the uniqueness of the current moment.

He tweeted: “The last 8 years of @asco are a blur in my memory. This year #ASCO was special, and I’m sure we will all remember where we were for this year’s meeting.”

Other oncologists praised the accessibility of the virtual meeting.

“The power of a virtual meeting is it creates an unlimited number of seats at the oncology research table. Anyone globally can be involved and that is really special,” said Suneel Kamath, MD, Cleveland Clinic, Ohio.

“Virtual ASCO levels the playing field for oncologists everywhere,” says Bishal Gyawali, MD, PhD, from Queen’s University, Kingston, Canada. In a Medscape Commentary, he notes that  “attending a typical ASCO meeting is astonishingly cost-prohibitive, especially for colleagues from low- and middle-income countries ... now everybody has the same access to the meeting.”

ASCO made the best out of a bad situation with the expanded virtual meeting, suggested David Henry, MD, Pennsylvania Hospital, Philadelphia, host of MDEdge’s Blood and Cancer podcast, part of the Medscape Professional Network. In an interview with ASCO president Skip Burris, MD, before the meeting, Henry said: “Making lemonade out of lemons. It’ll give us something new and different. What an amazing turn of events.”

With additional reporting by Zosia Chustecka , Liz Neporent, Neil Osterweil, and Jennifer Smith. This article first appeared on Medscape.com.