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An all-oral option for advanced HR+, HER2– breast cancer?
These results suggest tesetaxel plus capecitabine is “a potential new treatment option” for this patient population, said study investigator Joyce O’Shaughnessy, MD, of Baylor University Medical Center and Texas Oncology, both in Dallas.
“This should launch an oral taxane into the clinical space, which will be a nice addition to the toolbox for treating advanced breast cancer, with real upsides for patients,” said Hal Burstein, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, who was not involved in the trial but commented on the results in an interview.
Another commenter was more critical of CONTESSA’s results, which were presented at the 2020 San Antonio Breast Cancer Symposium.
“Three months’ difference in PFS in this setting is meaningless without overall survival [OS] results,” Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, said in a question submitted through the virtual meeting’s chat system.
At this point, the OS data are immature, and mature data won’t be available for another couple of years at least, according to the study’s protocol.
Dr. O’Shaughnessy defended the PFS result as being significant, however, saying it was comparable with outcomes seen previously with docetaxel-capecitabine and paclitaxel-gemcitabine combinations.
Other meeting attendees questioned why the waters had been muddied by testing the effects of tesetaxel in combination with capecitabine, albeit at a reduced dose, versus the approved full dose of capecitabine as monotherapy, particularly as a phase 2 trial had shown that tesetaxel demonstrated “significant activity” as monotherapy.
“The reason for the combination versus a monotherapy is because it was designed as a registration trial,” Dr. O’Shaughnessy explained. The trial was designed to be very similar to early taxane studies where docetaxel was assessed with or without capecitabine, or paclitaxel with or without gemcitabine.
“Probably we’re going to be using a doublet for patients who have virulent disease who really need a response,” Dr. O’Shaughnessy explained. She noted that the objective response rate was much higher with the tesetaxel-capecitabine combination than with capecitabine alone, and that result alone is “probably enough that we would utilize a doublet.”
The key thing is that it now gives patients an all-oral option, Dr. O’Shaughnessy said.
“The data are exciting because it would be terrific to have an orally available taxane chemotherapy,” agreed Dr. Burstein. “It is far more convenient for patients and opens access globally in places that do not have adequate resources for administration of IV therapeutics. Also, the data suggest that tesetaxel has a different side effect profile than IV taxane, with less neuropathy and less alopecia.”
Trial design
CONTESSA is an ongoing randomized, controlled trial that started in 2017 and is projected to end in early 2023. It is investigating the use of tesetaxel plus a reduced dose of capecitabine versus the approved dose of capecitabine alone in 685 women with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who had previously been treated with a taxane.
Being intrinsically orally bioavailable and more soluble than the other taxanes means that tesetaxel has a much longer half-life that allows for a “more convenient treatment experience for patients,” Dr. O’Shaughnessy observed.
Indeed, because tesetaxel only needs to be dosed once every 3 weeks, patients in the trial received tesetaxel at 27 mg/m2 only on the first day of a 21-day treatment cycle. This was combined with a reduced, 825-mg/m2 dose of capecitabine, given orally twice-daily on days 2-14 but once daily on the evening of day 1 and on the morning of day 15.
The combination regimen was compared with the recommended full dose of capecitabine alone, 1,250 mg/m2 given orally twice daily on days 2-14 but once daily on the evening of day 1 and on the morning of day 15.
Efficacy and safety
PFS was 9.8 months with tesetaxel plus capecitabine and 6.9 months with capecitabine alone, representing a 2.9-month improvement with the combination (hazard ratio, 0.716; P = .003).
A similar PFS benefit was seen regardless of multiple predefined subgroups, such as age, baseline performance status, duration of disease-free interval before study entry, and the use of CDK4/6 inhibitors.
The objective response rate was 57% with tesetaxel plus capecitabine and 41% with capecitabine alone (P = .0002). The 24-week disease control rate was 67% and 50%, respectively (P < .0001).
The most frequent treatment-emergent adverse event seen with the tesetaxel-capecitabine combination was neutropenia, occurring in 76.9% of patients, compared with 22.6% of patients in the monotherapy arm. Rates of grade 3-4 neutropenia were much higher in the combination arm (32.6% and 38.3%, respectively) than in the monotherapy arm (7.4% and 0.9%, respectively).
The neutropenia seen was “generally manageable,” Dr. O’Shaughnessy said, primarily with dose reductions and granulocyte colony–stimulating factor as needed.
She pointed out that rates of grade 3 or higher neuropathy and grade 2 alopecia were low, a respective 5.9% and 8%, with the combination.
The dose of capecitabine used in the control arm was noted to be higher than that used in usual practice.
“This was because of the global nature of the study and the regulatory requirements globally,” Dr. O’Shaughnessy said.
“The dose-modification scheme was that patients could have a dose reduction at the first sign of grade 2 toxicity,” she added, giving investigators the flexibility to reduce the dose as soon as possible.
This study was sponsored by Odonate Therapeutics. Dr. O’Shaughnessy disclosed consulting fees from AbbVie, Agendia, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, Genentech/Roche, Genomic Health, GRAIL, Heron, Immunomedics, Ipsen, Jounce, Lilly, Novartis, Odonate, Pfizer, Puma, and Seagen. Dr. Burstein and Dr. Cardoso had no relevant disclosures.
SOURCE: O’Shaughnessy J et al. SABCS 2020, Abstract GS4-01.
These results suggest tesetaxel plus capecitabine is “a potential new treatment option” for this patient population, said study investigator Joyce O’Shaughnessy, MD, of Baylor University Medical Center and Texas Oncology, both in Dallas.
“This should launch an oral taxane into the clinical space, which will be a nice addition to the toolbox for treating advanced breast cancer, with real upsides for patients,” said Hal Burstein, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, who was not involved in the trial but commented on the results in an interview.
Another commenter was more critical of CONTESSA’s results, which were presented at the 2020 San Antonio Breast Cancer Symposium.
“Three months’ difference in PFS in this setting is meaningless without overall survival [OS] results,” Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, said in a question submitted through the virtual meeting’s chat system.
At this point, the OS data are immature, and mature data won’t be available for another couple of years at least, according to the study’s protocol.
Dr. O’Shaughnessy defended the PFS result as being significant, however, saying it was comparable with outcomes seen previously with docetaxel-capecitabine and paclitaxel-gemcitabine combinations.
Other meeting attendees questioned why the waters had been muddied by testing the effects of tesetaxel in combination with capecitabine, albeit at a reduced dose, versus the approved full dose of capecitabine as monotherapy, particularly as a phase 2 trial had shown that tesetaxel demonstrated “significant activity” as monotherapy.
“The reason for the combination versus a monotherapy is because it was designed as a registration trial,” Dr. O’Shaughnessy explained. The trial was designed to be very similar to early taxane studies where docetaxel was assessed with or without capecitabine, or paclitaxel with or without gemcitabine.
“Probably we’re going to be using a doublet for patients who have virulent disease who really need a response,” Dr. O’Shaughnessy explained. She noted that the objective response rate was much higher with the tesetaxel-capecitabine combination than with capecitabine alone, and that result alone is “probably enough that we would utilize a doublet.”
The key thing is that it now gives patients an all-oral option, Dr. O’Shaughnessy said.
“The data are exciting because it would be terrific to have an orally available taxane chemotherapy,” agreed Dr. Burstein. “It is far more convenient for patients and opens access globally in places that do not have adequate resources for administration of IV therapeutics. Also, the data suggest that tesetaxel has a different side effect profile than IV taxane, with less neuropathy and less alopecia.”
Trial design
CONTESSA is an ongoing randomized, controlled trial that started in 2017 and is projected to end in early 2023. It is investigating the use of tesetaxel plus a reduced dose of capecitabine versus the approved dose of capecitabine alone in 685 women with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who had previously been treated with a taxane.
Being intrinsically orally bioavailable and more soluble than the other taxanes means that tesetaxel has a much longer half-life that allows for a “more convenient treatment experience for patients,” Dr. O’Shaughnessy observed.
Indeed, because tesetaxel only needs to be dosed once every 3 weeks, patients in the trial received tesetaxel at 27 mg/m2 only on the first day of a 21-day treatment cycle. This was combined with a reduced, 825-mg/m2 dose of capecitabine, given orally twice-daily on days 2-14 but once daily on the evening of day 1 and on the morning of day 15.
The combination regimen was compared with the recommended full dose of capecitabine alone, 1,250 mg/m2 given orally twice daily on days 2-14 but once daily on the evening of day 1 and on the morning of day 15.
Efficacy and safety
PFS was 9.8 months with tesetaxel plus capecitabine and 6.9 months with capecitabine alone, representing a 2.9-month improvement with the combination (hazard ratio, 0.716; P = .003).
A similar PFS benefit was seen regardless of multiple predefined subgroups, such as age, baseline performance status, duration of disease-free interval before study entry, and the use of CDK4/6 inhibitors.
The objective response rate was 57% with tesetaxel plus capecitabine and 41% with capecitabine alone (P = .0002). The 24-week disease control rate was 67% and 50%, respectively (P < .0001).
The most frequent treatment-emergent adverse event seen with the tesetaxel-capecitabine combination was neutropenia, occurring in 76.9% of patients, compared with 22.6% of patients in the monotherapy arm. Rates of grade 3-4 neutropenia were much higher in the combination arm (32.6% and 38.3%, respectively) than in the monotherapy arm (7.4% and 0.9%, respectively).
The neutropenia seen was “generally manageable,” Dr. O’Shaughnessy said, primarily with dose reductions and granulocyte colony–stimulating factor as needed.
She pointed out that rates of grade 3 or higher neuropathy and grade 2 alopecia were low, a respective 5.9% and 8%, with the combination.
The dose of capecitabine used in the control arm was noted to be higher than that used in usual practice.
“This was because of the global nature of the study and the regulatory requirements globally,” Dr. O’Shaughnessy said.
“The dose-modification scheme was that patients could have a dose reduction at the first sign of grade 2 toxicity,” she added, giving investigators the flexibility to reduce the dose as soon as possible.
This study was sponsored by Odonate Therapeutics. Dr. O’Shaughnessy disclosed consulting fees from AbbVie, Agendia, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, Genentech/Roche, Genomic Health, GRAIL, Heron, Immunomedics, Ipsen, Jounce, Lilly, Novartis, Odonate, Pfizer, Puma, and Seagen. Dr. Burstein and Dr. Cardoso had no relevant disclosures.
SOURCE: O’Shaughnessy J et al. SABCS 2020, Abstract GS4-01.
These results suggest tesetaxel plus capecitabine is “a potential new treatment option” for this patient population, said study investigator Joyce O’Shaughnessy, MD, of Baylor University Medical Center and Texas Oncology, both in Dallas.
“This should launch an oral taxane into the clinical space, which will be a nice addition to the toolbox for treating advanced breast cancer, with real upsides for patients,” said Hal Burstein, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, who was not involved in the trial but commented on the results in an interview.
Another commenter was more critical of CONTESSA’s results, which were presented at the 2020 San Antonio Breast Cancer Symposium.
“Three months’ difference in PFS in this setting is meaningless without overall survival [OS] results,” Fatima Cardoso, MD, of Champalimaud Clinical Center in Lisbon, Portugal, said in a question submitted through the virtual meeting’s chat system.
At this point, the OS data are immature, and mature data won’t be available for another couple of years at least, according to the study’s protocol.
Dr. O’Shaughnessy defended the PFS result as being significant, however, saying it was comparable with outcomes seen previously with docetaxel-capecitabine and paclitaxel-gemcitabine combinations.
Other meeting attendees questioned why the waters had been muddied by testing the effects of tesetaxel in combination with capecitabine, albeit at a reduced dose, versus the approved full dose of capecitabine as monotherapy, particularly as a phase 2 trial had shown that tesetaxel demonstrated “significant activity” as monotherapy.
“The reason for the combination versus a monotherapy is because it was designed as a registration trial,” Dr. O’Shaughnessy explained. The trial was designed to be very similar to early taxane studies where docetaxel was assessed with or without capecitabine, or paclitaxel with or without gemcitabine.
“Probably we’re going to be using a doublet for patients who have virulent disease who really need a response,” Dr. O’Shaughnessy explained. She noted that the objective response rate was much higher with the tesetaxel-capecitabine combination than with capecitabine alone, and that result alone is “probably enough that we would utilize a doublet.”
The key thing is that it now gives patients an all-oral option, Dr. O’Shaughnessy said.
“The data are exciting because it would be terrific to have an orally available taxane chemotherapy,” agreed Dr. Burstein. “It is far more convenient for patients and opens access globally in places that do not have adequate resources for administration of IV therapeutics. Also, the data suggest that tesetaxel has a different side effect profile than IV taxane, with less neuropathy and less alopecia.”
Trial design
CONTESSA is an ongoing randomized, controlled trial that started in 2017 and is projected to end in early 2023. It is investigating the use of tesetaxel plus a reduced dose of capecitabine versus the approved dose of capecitabine alone in 685 women with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who had previously been treated with a taxane.
Being intrinsically orally bioavailable and more soluble than the other taxanes means that tesetaxel has a much longer half-life that allows for a “more convenient treatment experience for patients,” Dr. O’Shaughnessy observed.
Indeed, because tesetaxel only needs to be dosed once every 3 weeks, patients in the trial received tesetaxel at 27 mg/m2 only on the first day of a 21-day treatment cycle. This was combined with a reduced, 825-mg/m2 dose of capecitabine, given orally twice-daily on days 2-14 but once daily on the evening of day 1 and on the morning of day 15.
The combination regimen was compared with the recommended full dose of capecitabine alone, 1,250 mg/m2 given orally twice daily on days 2-14 but once daily on the evening of day 1 and on the morning of day 15.
Efficacy and safety
PFS was 9.8 months with tesetaxel plus capecitabine and 6.9 months with capecitabine alone, representing a 2.9-month improvement with the combination (hazard ratio, 0.716; P = .003).
A similar PFS benefit was seen regardless of multiple predefined subgroups, such as age, baseline performance status, duration of disease-free interval before study entry, and the use of CDK4/6 inhibitors.
The objective response rate was 57% with tesetaxel plus capecitabine and 41% with capecitabine alone (P = .0002). The 24-week disease control rate was 67% and 50%, respectively (P < .0001).
The most frequent treatment-emergent adverse event seen with the tesetaxel-capecitabine combination was neutropenia, occurring in 76.9% of patients, compared with 22.6% of patients in the monotherapy arm. Rates of grade 3-4 neutropenia were much higher in the combination arm (32.6% and 38.3%, respectively) than in the monotherapy arm (7.4% and 0.9%, respectively).
The neutropenia seen was “generally manageable,” Dr. O’Shaughnessy said, primarily with dose reductions and granulocyte colony–stimulating factor as needed.
She pointed out that rates of grade 3 or higher neuropathy and grade 2 alopecia were low, a respective 5.9% and 8%, with the combination.
The dose of capecitabine used in the control arm was noted to be higher than that used in usual practice.
“This was because of the global nature of the study and the regulatory requirements globally,” Dr. O’Shaughnessy said.
“The dose-modification scheme was that patients could have a dose reduction at the first sign of grade 2 toxicity,” she added, giving investigators the flexibility to reduce the dose as soon as possible.
This study was sponsored by Odonate Therapeutics. Dr. O’Shaughnessy disclosed consulting fees from AbbVie, Agendia, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, Genentech/Roche, Genomic Health, GRAIL, Heron, Immunomedics, Ipsen, Jounce, Lilly, Novartis, Odonate, Pfizer, Puma, and Seagen. Dr. Burstein and Dr. Cardoso had no relevant disclosures.
SOURCE: O’Shaughnessy J et al. SABCS 2020, Abstract GS4-01.
FROM SABCS 2020
Pembro benefits in mTNBC regardless of chemo type
Adding pembrolizumab to chemotherapy substantially increases progression-free survival (PFS) in treatment-naive advanced or metastatic triple-negative breast cancer (TNBC) regardless of chemotherapy type, suggests an analysis of the clinical trial KEYNOTE-355.
There was also a trend for improved outcomes with increasing programmed death–ligand 1 (PD-L1) expression in the tumor, as measured by combined positive score (CPS).
“These data further support a role for the addition of pembro to standard chemo for the first-line treatment of metastatic TNBC,” said study presenter Hope S. Rugo, MD, from the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
The research was presented at the 2020 San Antonio Breast Cancer Symposium on Dec. 10.
Last month, pembrolizumab was granted accelerated approval by the Food and Drug Administration in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10).
The approval was based on data from KEYNOTE-355, which involved almost 850 women with previously untreated locally recurrent inoperable or metastatic TNBC randomized 2:1 to pembrolizumab plus investigator’s choice of chemotherapy who were followed for 2 years.
For the current analysis, patients were stratified by PD-L1 CPS in the tumor, including over 320 patients with CPS ≥10, and by accompanying chemotherapy regimen.
In the overall intention-to-treat (ITT) population (n = 847), median PFS was longer with pembrolizumab plus chemotherapy versus placebo plus chemotherapy, at 9.7 months versus 5.6 months (hazard ratio, 0.82).
PFS improved step-wise with increased PD-L1 expression. In patients with PD-L1 CPS ≥1, the HR was 0.74, and in those with PD-L1 CPS ≥10, it was 0.65.
A similar incremental improvement by PD-L1 expression was seen in the overall response rate, with the rate topping out at 53.2% in the pembrolizumab plus chemotherapy arm, among the PD-L1 CPS ≥10 group.
Duration of response told a similar story, with the pembro-chemo combination providing superior results and the treatment effect increasing with PD-L1 enrichment.
Study discussant Sylvia Adams, MD, New York University Perlmutter Cancer Center, New York, said the “consistency of treatment effect” with different chemotherapy backbones seen in the study is “very important, as it is currently unknown what the optimal backbone is.”
She also noted that the chemotherapy analysis presented by Dr. Rugo was “exploratory” and “not powered to show the winner of the chemotherapy backbone.”
Nevertheless, in the postpresentation debate, Ian Krop, MD, PhD, Dana-Farber Cancer Institute, Boston, said that there are “several questions over the chemotherapy partner,” including whether there were differences in the populations who received each type of regimen.
Dr. Rugo replied that “because the trial wasn’t powered to look at the separate chemotherapy groups with any statistical significance ... it’s really impossible to draw any specific conclusions because it’s the overall population that’s evaluated.”
Asked about when overall survival results will be presented, Dr. Rugo said that “everybody is very interested” in that, “and we expect these results to be available next year.”
Study details
For KEYNOTE-355, researchers recruited women with previously untreated metastatic TNBC who had completed treatment with curative intent ≥6 months prior to their first disease recurrence.
They were randomized 2:1 to pembrolizumab or placebo plus investigator’s choice of chemotherapy from nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin for up to 35 administrations of pembrolizumab or placebo or until progression, intolerable toxicity, or cessation of treatment.
Crossover was not allowed. Patients were stratified by type of chemotherapy, PD-L1 expression in the tumor, and prior treatment in the neoadjuvant or adjuvant setting with the same class of chemotherapy.
Response was assessed with imaging every 8 weeks until week 24, then every 9 weeks during the first year of follow-up, and then every 12 weeks.
Of 847 randomized patients, 566 received pembrolizumab plus chemotherapy and 281 were assigned to the placebo group. The median age was 53 years in both groups.
The majority (75.1%) of patients in both groups were PD-L1 positive with a centrally assessed CPS ≥1, while 38.9% of patients in the pembrolizumab arm and 36.7% of those given placebo had a CPS ≥10.
After a median follow-up of 25.9 months, 16 patients given pembrolizumab had completed the study and 33 were still ongoing.
This compares with five patients having completed the placebo arm, and 12 still ongoing, after a median follow-up of 26.3 months.
The overall response rate was higher with pembrolizumab plus chemotherapy in the ITT population, at 41.0% versus 35.9%, rising to 45.2% versus 37.9% in patients with PD-L1 CPS ≥1 and 53.2% versus 39.8% in the PD-L1 CPS ≥10 group.
Again, when the groups were stratified by on-study chemotherapy, the overall response rate was higher with pembrolizumab versus placebo regardless of the chemotherapy partner.
Finally, the duration of response with pembrolizumab plus chemotherapy was longer than that seen with placebo, at a median of 10.1 months versus 6.4 months in the ITT population.
In the PD-L1 CPS ≥1 group, the duration of response was 10.1 months versus 6.5 months, rising to 19.3 months versus 7.3 months in the PD-L1 CPS ≥10 group.
Dr. Adams nevertheless said that PD-L1 remains an “imperfect” biomarker in metastatic TNBC, although it is “the best to date.” Furthermore, the IMpassion130 trial, featuring atezolizumab, showed that there is “very poor” analytic and clinical concordance between assays, which “complicates clinical decision-making.”
This study was sponsored by Merck. Dr. Rugo, Dr. Adams, and Dr. Krop have disclosed financial ties to multiple pharmaceutical companies, including Merck.
A version of this article first appeared on Medscape.com.
Adding pembrolizumab to chemotherapy substantially increases progression-free survival (PFS) in treatment-naive advanced or metastatic triple-negative breast cancer (TNBC) regardless of chemotherapy type, suggests an analysis of the clinical trial KEYNOTE-355.
There was also a trend for improved outcomes with increasing programmed death–ligand 1 (PD-L1) expression in the tumor, as measured by combined positive score (CPS).
“These data further support a role for the addition of pembro to standard chemo for the first-line treatment of metastatic TNBC,” said study presenter Hope S. Rugo, MD, from the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
The research was presented at the 2020 San Antonio Breast Cancer Symposium on Dec. 10.
Last month, pembrolizumab was granted accelerated approval by the Food and Drug Administration in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10).
The approval was based on data from KEYNOTE-355, which involved almost 850 women with previously untreated locally recurrent inoperable or metastatic TNBC randomized 2:1 to pembrolizumab plus investigator’s choice of chemotherapy who were followed for 2 years.
For the current analysis, patients were stratified by PD-L1 CPS in the tumor, including over 320 patients with CPS ≥10, and by accompanying chemotherapy regimen.
In the overall intention-to-treat (ITT) population (n = 847), median PFS was longer with pembrolizumab plus chemotherapy versus placebo plus chemotherapy, at 9.7 months versus 5.6 months (hazard ratio, 0.82).
PFS improved step-wise with increased PD-L1 expression. In patients with PD-L1 CPS ≥1, the HR was 0.74, and in those with PD-L1 CPS ≥10, it was 0.65.
A similar incremental improvement by PD-L1 expression was seen in the overall response rate, with the rate topping out at 53.2% in the pembrolizumab plus chemotherapy arm, among the PD-L1 CPS ≥10 group.
Duration of response told a similar story, with the pembro-chemo combination providing superior results and the treatment effect increasing with PD-L1 enrichment.
Study discussant Sylvia Adams, MD, New York University Perlmutter Cancer Center, New York, said the “consistency of treatment effect” with different chemotherapy backbones seen in the study is “very important, as it is currently unknown what the optimal backbone is.”
She also noted that the chemotherapy analysis presented by Dr. Rugo was “exploratory” and “not powered to show the winner of the chemotherapy backbone.”
Nevertheless, in the postpresentation debate, Ian Krop, MD, PhD, Dana-Farber Cancer Institute, Boston, said that there are “several questions over the chemotherapy partner,” including whether there were differences in the populations who received each type of regimen.
Dr. Rugo replied that “because the trial wasn’t powered to look at the separate chemotherapy groups with any statistical significance ... it’s really impossible to draw any specific conclusions because it’s the overall population that’s evaluated.”
Asked about when overall survival results will be presented, Dr. Rugo said that “everybody is very interested” in that, “and we expect these results to be available next year.”
Study details
For KEYNOTE-355, researchers recruited women with previously untreated metastatic TNBC who had completed treatment with curative intent ≥6 months prior to their first disease recurrence.
They were randomized 2:1 to pembrolizumab or placebo plus investigator’s choice of chemotherapy from nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin for up to 35 administrations of pembrolizumab or placebo or until progression, intolerable toxicity, or cessation of treatment.
Crossover was not allowed. Patients were stratified by type of chemotherapy, PD-L1 expression in the tumor, and prior treatment in the neoadjuvant or adjuvant setting with the same class of chemotherapy.
Response was assessed with imaging every 8 weeks until week 24, then every 9 weeks during the first year of follow-up, and then every 12 weeks.
Of 847 randomized patients, 566 received pembrolizumab plus chemotherapy and 281 were assigned to the placebo group. The median age was 53 years in both groups.
The majority (75.1%) of patients in both groups were PD-L1 positive with a centrally assessed CPS ≥1, while 38.9% of patients in the pembrolizumab arm and 36.7% of those given placebo had a CPS ≥10.
After a median follow-up of 25.9 months, 16 patients given pembrolizumab had completed the study and 33 were still ongoing.
This compares with five patients having completed the placebo arm, and 12 still ongoing, after a median follow-up of 26.3 months.
The overall response rate was higher with pembrolizumab plus chemotherapy in the ITT population, at 41.0% versus 35.9%, rising to 45.2% versus 37.9% in patients with PD-L1 CPS ≥1 and 53.2% versus 39.8% in the PD-L1 CPS ≥10 group.
Again, when the groups were stratified by on-study chemotherapy, the overall response rate was higher with pembrolizumab versus placebo regardless of the chemotherapy partner.
Finally, the duration of response with pembrolizumab plus chemotherapy was longer than that seen with placebo, at a median of 10.1 months versus 6.4 months in the ITT population.
In the PD-L1 CPS ≥1 group, the duration of response was 10.1 months versus 6.5 months, rising to 19.3 months versus 7.3 months in the PD-L1 CPS ≥10 group.
Dr. Adams nevertheless said that PD-L1 remains an “imperfect” biomarker in metastatic TNBC, although it is “the best to date.” Furthermore, the IMpassion130 trial, featuring atezolizumab, showed that there is “very poor” analytic and clinical concordance between assays, which “complicates clinical decision-making.”
This study was sponsored by Merck. Dr. Rugo, Dr. Adams, and Dr. Krop have disclosed financial ties to multiple pharmaceutical companies, including Merck.
A version of this article first appeared on Medscape.com.
Adding pembrolizumab to chemotherapy substantially increases progression-free survival (PFS) in treatment-naive advanced or metastatic triple-negative breast cancer (TNBC) regardless of chemotherapy type, suggests an analysis of the clinical trial KEYNOTE-355.
There was also a trend for improved outcomes with increasing programmed death–ligand 1 (PD-L1) expression in the tumor, as measured by combined positive score (CPS).
“These data further support a role for the addition of pembro to standard chemo for the first-line treatment of metastatic TNBC,” said study presenter Hope S. Rugo, MD, from the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco.
The research was presented at the 2020 San Antonio Breast Cancer Symposium on Dec. 10.
Last month, pembrolizumab was granted accelerated approval by the Food and Drug Administration in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10).
The approval was based on data from KEYNOTE-355, which involved almost 850 women with previously untreated locally recurrent inoperable or metastatic TNBC randomized 2:1 to pembrolizumab plus investigator’s choice of chemotherapy who were followed for 2 years.
For the current analysis, patients were stratified by PD-L1 CPS in the tumor, including over 320 patients with CPS ≥10, and by accompanying chemotherapy regimen.
In the overall intention-to-treat (ITT) population (n = 847), median PFS was longer with pembrolizumab plus chemotherapy versus placebo plus chemotherapy, at 9.7 months versus 5.6 months (hazard ratio, 0.82).
PFS improved step-wise with increased PD-L1 expression. In patients with PD-L1 CPS ≥1, the HR was 0.74, and in those with PD-L1 CPS ≥10, it was 0.65.
A similar incremental improvement by PD-L1 expression was seen in the overall response rate, with the rate topping out at 53.2% in the pembrolizumab plus chemotherapy arm, among the PD-L1 CPS ≥10 group.
Duration of response told a similar story, with the pembro-chemo combination providing superior results and the treatment effect increasing with PD-L1 enrichment.
Study discussant Sylvia Adams, MD, New York University Perlmutter Cancer Center, New York, said the “consistency of treatment effect” with different chemotherapy backbones seen in the study is “very important, as it is currently unknown what the optimal backbone is.”
She also noted that the chemotherapy analysis presented by Dr. Rugo was “exploratory” and “not powered to show the winner of the chemotherapy backbone.”
Nevertheless, in the postpresentation debate, Ian Krop, MD, PhD, Dana-Farber Cancer Institute, Boston, said that there are “several questions over the chemotherapy partner,” including whether there were differences in the populations who received each type of regimen.
Dr. Rugo replied that “because the trial wasn’t powered to look at the separate chemotherapy groups with any statistical significance ... it’s really impossible to draw any specific conclusions because it’s the overall population that’s evaluated.”
Asked about when overall survival results will be presented, Dr. Rugo said that “everybody is very interested” in that, “and we expect these results to be available next year.”
Study details
For KEYNOTE-355, researchers recruited women with previously untreated metastatic TNBC who had completed treatment with curative intent ≥6 months prior to their first disease recurrence.
They were randomized 2:1 to pembrolizumab or placebo plus investigator’s choice of chemotherapy from nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin for up to 35 administrations of pembrolizumab or placebo or until progression, intolerable toxicity, or cessation of treatment.
Crossover was not allowed. Patients were stratified by type of chemotherapy, PD-L1 expression in the tumor, and prior treatment in the neoadjuvant or adjuvant setting with the same class of chemotherapy.
Response was assessed with imaging every 8 weeks until week 24, then every 9 weeks during the first year of follow-up, and then every 12 weeks.
Of 847 randomized patients, 566 received pembrolizumab plus chemotherapy and 281 were assigned to the placebo group. The median age was 53 years in both groups.
The majority (75.1%) of patients in both groups were PD-L1 positive with a centrally assessed CPS ≥1, while 38.9% of patients in the pembrolizumab arm and 36.7% of those given placebo had a CPS ≥10.
After a median follow-up of 25.9 months, 16 patients given pembrolizumab had completed the study and 33 were still ongoing.
This compares with five patients having completed the placebo arm, and 12 still ongoing, after a median follow-up of 26.3 months.
The overall response rate was higher with pembrolizumab plus chemotherapy in the ITT population, at 41.0% versus 35.9%, rising to 45.2% versus 37.9% in patients with PD-L1 CPS ≥1 and 53.2% versus 39.8% in the PD-L1 CPS ≥10 group.
Again, when the groups were stratified by on-study chemotherapy, the overall response rate was higher with pembrolizumab versus placebo regardless of the chemotherapy partner.
Finally, the duration of response with pembrolizumab plus chemotherapy was longer than that seen with placebo, at a median of 10.1 months versus 6.4 months in the ITT population.
In the PD-L1 CPS ≥1 group, the duration of response was 10.1 months versus 6.5 months, rising to 19.3 months versus 7.3 months in the PD-L1 CPS ≥10 group.
Dr. Adams nevertheless said that PD-L1 remains an “imperfect” biomarker in metastatic TNBC, although it is “the best to date.” Furthermore, the IMpassion130 trial, featuring atezolizumab, showed that there is “very poor” analytic and clinical concordance between assays, which “complicates clinical decision-making.”
This study was sponsored by Merck. Dr. Rugo, Dr. Adams, and Dr. Krop have disclosed financial ties to multiple pharmaceutical companies, including Merck.
A version of this article first appeared on Medscape.com.
First-in-class ADC has benefit across mTNBC subgroups
But both an observer and the lead study author cautioned that the results were hypothesis generating.
Nonetheless, the data suggest the drug yields good survival outcomes in comparison with placebo in both BRCA1/2-positive and -negative patients and is effective even for those with low expression of the target protein, trophoblast cell surface antigen 2 (Trop-2).
The research was presented at the San Antonio Breast Cancer Symposium (SABCS) 2020.
Study presenter Sara Hurvitz, MD, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, urged caution in interpreting the data, given the small sample sizes in the Trop-2–low subgroup and germline BRCA1/2-positive subgroup.
Jennifer K. Litton, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, who was not involved in the research, echoed those comments.
She told Medscape Medical News that the numbers, particularly for the BRCA1/2 analysis, were “very small.”
She added: “This was not a prespecified group, so it represents an interesting analysis to be hypothesis generating for future studies but not anything applicable to current clinical practice.”
Nevertheless, Litton said the data from the primary analysis of ASCENT remain “practice changing” for women with mTNBC who have received at least two previous lines of therapy.
As to whether SG will eventually move beyond this advanced setting, she emphasized that “more trials would need to be done and reported evaluating its role in other settings, and hopefully expanding its usefulness for patients.”
SG is a first-in-class drug comprising an antibody directed at Trop-2, which is highly expressed in breast cancer, and linked to SN-38, the active metabolite of irinotecan.
On the basis of positive phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with mTNBC who experience disease progression after at least two prior therapies.
As reported by Medscape Medical News, primary results from ASCENT that were presented at ESMO 2020 showed that SG improved progression-free survival (PFS) by nearly 4 months and overall survival by more than 5 months for women with pretreated mTNBC compared to chemotherapy.
Study details
At SABCS, Hurvitz presented an exploratory biomarker evaluation of data from the trial regarding the association between SG efficacy and Trop-2 expression, as well as germline BRCA1/2 mutation status.
She reminded the audience that, in ASCENT, 529 patients with mTNBC who had experienced disease progression after undergoing at least two chemotherapy regimens for advanced disease were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or physician’s choice of treatment.
Treatment was continued until disease progression or unacceptable toxicity occurred.
For the current analysis, which focused on patients who did not have brain metastases, the team studied primary or metastatic archival biopsy or surgical specimens collected at study entry.
These were analyzed using a validated immunohistochemistry assay. Tumors were categorized as Trop-2–low, –medium, or –-high expressers on the basis of H-score, which is a weighted summation of percent staining. In addition, germline BRCA1/2 mutation status was determined at baseline.
Mutation status was known for 149 SG patients and 143 control patients. Of those, the majority (57% and 54%, respectively) were BRCA1/2 negative.
Among 151 SG patients for whom Trop-2 expression status was available, 56% had tumors of high expression; 26%, medium expression; and 18%, low expression. In the control group, Trop-2 expression was known in 139 patients, of whom 52% had tumors of high expression; 25%, medium expression; and 23%, low expression.
Hurvitz reported that, although median PFS among patients given SG decreased with decreasing Trop-2 expression, it remained longer than that seen with control treatment. In patients with tumors of Trop-2–high status, median PFS was 6.9 months with SG, vs. 2.5 for patients who underwent control treatment. This fell to 5.6 months vs. 2.2 months in the Trop-2–medium group and 2.7 months vs 1.6 months in Trop-2–low group.
A similar pattern was seen for overall survival. In the Trop-2–high group, median overall survival was 14.2 months with SG, vs. 6.9 months with control therapy; 14.9 months vs. 6.9 months in the Trop-2–medium group; and 9.3 months vs. 7.6 months in the Trop-2–low group.
Again, the objective response rate fell from 44% to 38% and then to 22% with SG in the Trop-2–high, –medium, and –low groups, compared with 1%, 11%, and 6%, respectively, with control treatment.
There did not seem to be any interaction between Trop-2 expression and treatment-related adverse events of special interest. Rates of neutropenia, diarrhea, and anemia were consistently higher in SG-treated patients than in those given placebo.
Hurvitz said the objective response rate was markedly higher with SG vs. control treatment in both BRCA1/2-positive and -negative patients, at 19% vs. 6% in the positive group and 33% vs. 6% in the negative group.
This was reflected in improved median PFS with SG in both subgroups, at 4.6 months vs. 2.5 months with control therapy in BRCA1/2-positive patients and 4.9 months vs. 1.6 months in BRCA1/2-negative patients.
Overall survival was 15.6 months with SG, vs. 4.4 months with control treatment in BRCA1/2-positive patients. In BRCA1/2-negative patients, the respective figures were 10.9 months and 7.0 months.
The study was sponsored by Immunomedics. Hurvitz has financial ties to Immunomedics and multiple other pharmaceutical companies. Litton has financial ties to multiple companies, including Medscape and companies developing and marketing breast cancer therapies.
This article first appeared on Medscape.com.
But both an observer and the lead study author cautioned that the results were hypothesis generating.
Nonetheless, the data suggest the drug yields good survival outcomes in comparison with placebo in both BRCA1/2-positive and -negative patients and is effective even for those with low expression of the target protein, trophoblast cell surface antigen 2 (Trop-2).
The research was presented at the San Antonio Breast Cancer Symposium (SABCS) 2020.
Study presenter Sara Hurvitz, MD, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, urged caution in interpreting the data, given the small sample sizes in the Trop-2–low subgroup and germline BRCA1/2-positive subgroup.
Jennifer K. Litton, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, who was not involved in the research, echoed those comments.
She told Medscape Medical News that the numbers, particularly for the BRCA1/2 analysis, were “very small.”
She added: “This was not a prespecified group, so it represents an interesting analysis to be hypothesis generating for future studies but not anything applicable to current clinical practice.”
Nevertheless, Litton said the data from the primary analysis of ASCENT remain “practice changing” for women with mTNBC who have received at least two previous lines of therapy.
As to whether SG will eventually move beyond this advanced setting, she emphasized that “more trials would need to be done and reported evaluating its role in other settings, and hopefully expanding its usefulness for patients.”
SG is a first-in-class drug comprising an antibody directed at Trop-2, which is highly expressed in breast cancer, and linked to SN-38, the active metabolite of irinotecan.
On the basis of positive phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with mTNBC who experience disease progression after at least two prior therapies.
As reported by Medscape Medical News, primary results from ASCENT that were presented at ESMO 2020 showed that SG improved progression-free survival (PFS) by nearly 4 months and overall survival by more than 5 months for women with pretreated mTNBC compared to chemotherapy.
Study details
At SABCS, Hurvitz presented an exploratory biomarker evaluation of data from the trial regarding the association between SG efficacy and Trop-2 expression, as well as germline BRCA1/2 mutation status.
She reminded the audience that, in ASCENT, 529 patients with mTNBC who had experienced disease progression after undergoing at least two chemotherapy regimens for advanced disease were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or physician’s choice of treatment.
Treatment was continued until disease progression or unacceptable toxicity occurred.
For the current analysis, which focused on patients who did not have brain metastases, the team studied primary or metastatic archival biopsy or surgical specimens collected at study entry.
These were analyzed using a validated immunohistochemistry assay. Tumors were categorized as Trop-2–low, –medium, or –-high expressers on the basis of H-score, which is a weighted summation of percent staining. In addition, germline BRCA1/2 mutation status was determined at baseline.
Mutation status was known for 149 SG patients and 143 control patients. Of those, the majority (57% and 54%, respectively) were BRCA1/2 negative.
Among 151 SG patients for whom Trop-2 expression status was available, 56% had tumors of high expression; 26%, medium expression; and 18%, low expression. In the control group, Trop-2 expression was known in 139 patients, of whom 52% had tumors of high expression; 25%, medium expression; and 23%, low expression.
Hurvitz reported that, although median PFS among patients given SG decreased with decreasing Trop-2 expression, it remained longer than that seen with control treatment. In patients with tumors of Trop-2–high status, median PFS was 6.9 months with SG, vs. 2.5 for patients who underwent control treatment. This fell to 5.6 months vs. 2.2 months in the Trop-2–medium group and 2.7 months vs 1.6 months in Trop-2–low group.
A similar pattern was seen for overall survival. In the Trop-2–high group, median overall survival was 14.2 months with SG, vs. 6.9 months with control therapy; 14.9 months vs. 6.9 months in the Trop-2–medium group; and 9.3 months vs. 7.6 months in the Trop-2–low group.
Again, the objective response rate fell from 44% to 38% and then to 22% with SG in the Trop-2–high, –medium, and –low groups, compared with 1%, 11%, and 6%, respectively, with control treatment.
There did not seem to be any interaction between Trop-2 expression and treatment-related adverse events of special interest. Rates of neutropenia, diarrhea, and anemia were consistently higher in SG-treated patients than in those given placebo.
Hurvitz said the objective response rate was markedly higher with SG vs. control treatment in both BRCA1/2-positive and -negative patients, at 19% vs. 6% in the positive group and 33% vs. 6% in the negative group.
This was reflected in improved median PFS with SG in both subgroups, at 4.6 months vs. 2.5 months with control therapy in BRCA1/2-positive patients and 4.9 months vs. 1.6 months in BRCA1/2-negative patients.
Overall survival was 15.6 months with SG, vs. 4.4 months with control treatment in BRCA1/2-positive patients. In BRCA1/2-negative patients, the respective figures were 10.9 months and 7.0 months.
The study was sponsored by Immunomedics. Hurvitz has financial ties to Immunomedics and multiple other pharmaceutical companies. Litton has financial ties to multiple companies, including Medscape and companies developing and marketing breast cancer therapies.
This article first appeared on Medscape.com.
But both an observer and the lead study author cautioned that the results were hypothesis generating.
Nonetheless, the data suggest the drug yields good survival outcomes in comparison with placebo in both BRCA1/2-positive and -negative patients and is effective even for those with low expression of the target protein, trophoblast cell surface antigen 2 (Trop-2).
The research was presented at the San Antonio Breast Cancer Symposium (SABCS) 2020.
Study presenter Sara Hurvitz, MD, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, urged caution in interpreting the data, given the small sample sizes in the Trop-2–low subgroup and germline BRCA1/2-positive subgroup.
Jennifer K. Litton, MD, University of Texas MD Anderson Cancer Center, Houston, Texas, who was not involved in the research, echoed those comments.
She told Medscape Medical News that the numbers, particularly for the BRCA1/2 analysis, were “very small.”
She added: “This was not a prespecified group, so it represents an interesting analysis to be hypothesis generating for future studies but not anything applicable to current clinical practice.”
Nevertheless, Litton said the data from the primary analysis of ASCENT remain “practice changing” for women with mTNBC who have received at least two previous lines of therapy.
As to whether SG will eventually move beyond this advanced setting, she emphasized that “more trials would need to be done and reported evaluating its role in other settings, and hopefully expanding its usefulness for patients.”
SG is a first-in-class drug comprising an antibody directed at Trop-2, which is highly expressed in breast cancer, and linked to SN-38, the active metabolite of irinotecan.
On the basis of positive phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with mTNBC who experience disease progression after at least two prior therapies.
As reported by Medscape Medical News, primary results from ASCENT that were presented at ESMO 2020 showed that SG improved progression-free survival (PFS) by nearly 4 months and overall survival by more than 5 months for women with pretreated mTNBC compared to chemotherapy.
Study details
At SABCS, Hurvitz presented an exploratory biomarker evaluation of data from the trial regarding the association between SG efficacy and Trop-2 expression, as well as germline BRCA1/2 mutation status.
She reminded the audience that, in ASCENT, 529 patients with mTNBC who had experienced disease progression after undergoing at least two chemotherapy regimens for advanced disease were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or physician’s choice of treatment.
Treatment was continued until disease progression or unacceptable toxicity occurred.
For the current analysis, which focused on patients who did not have brain metastases, the team studied primary or metastatic archival biopsy or surgical specimens collected at study entry.
These were analyzed using a validated immunohistochemistry assay. Tumors were categorized as Trop-2–low, –medium, or –-high expressers on the basis of H-score, which is a weighted summation of percent staining. In addition, germline BRCA1/2 mutation status was determined at baseline.
Mutation status was known for 149 SG patients and 143 control patients. Of those, the majority (57% and 54%, respectively) were BRCA1/2 negative.
Among 151 SG patients for whom Trop-2 expression status was available, 56% had tumors of high expression; 26%, medium expression; and 18%, low expression. In the control group, Trop-2 expression was known in 139 patients, of whom 52% had tumors of high expression; 25%, medium expression; and 23%, low expression.
Hurvitz reported that, although median PFS among patients given SG decreased with decreasing Trop-2 expression, it remained longer than that seen with control treatment. In patients with tumors of Trop-2–high status, median PFS was 6.9 months with SG, vs. 2.5 for patients who underwent control treatment. This fell to 5.6 months vs. 2.2 months in the Trop-2–medium group and 2.7 months vs 1.6 months in Trop-2–low group.
A similar pattern was seen for overall survival. In the Trop-2–high group, median overall survival was 14.2 months with SG, vs. 6.9 months with control therapy; 14.9 months vs. 6.9 months in the Trop-2–medium group; and 9.3 months vs. 7.6 months in the Trop-2–low group.
Again, the objective response rate fell from 44% to 38% and then to 22% with SG in the Trop-2–high, –medium, and –low groups, compared with 1%, 11%, and 6%, respectively, with control treatment.
There did not seem to be any interaction between Trop-2 expression and treatment-related adverse events of special interest. Rates of neutropenia, diarrhea, and anemia were consistently higher in SG-treated patients than in those given placebo.
Hurvitz said the objective response rate was markedly higher with SG vs. control treatment in both BRCA1/2-positive and -negative patients, at 19% vs. 6% in the positive group and 33% vs. 6% in the negative group.
This was reflected in improved median PFS with SG in both subgroups, at 4.6 months vs. 2.5 months with control therapy in BRCA1/2-positive patients and 4.9 months vs. 1.6 months in BRCA1/2-negative patients.
Overall survival was 15.6 months with SG, vs. 4.4 months with control treatment in BRCA1/2-positive patients. In BRCA1/2-negative patients, the respective figures were 10.9 months and 7.0 months.
The study was sponsored by Immunomedics. Hurvitz has financial ties to Immunomedics and multiple other pharmaceutical companies. Litton has financial ties to multiple companies, including Medscape and companies developing and marketing breast cancer therapies.
This article first appeared on Medscape.com.
FROM SABCS 2020
CTCs predict overall survival in metastatic breast cancer
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
The CTC results are available about 4 weeks after start of therapy. Conventional imaging is carried out after about 3 months.
But an expert is not convinced that this approach is currently ready for clinical use and suggests that, for now, it should remain a tool for use in research.
The new meta-analysis, which involved data on more than 4000 patients, showed that the presence or the absence of CTCs “strongly” predicts overall survival (OS).
Median OS was greatest (47 months) for patients who had no CTCs at baseline and at follow-up. In contrast, the median OS was shortest (17.8 months) for patients who had CTCs at both time points.
The risk for death was more than 200% greater for patients in the latter group than in the former group.
The results “suggest the potential for clinical utility” of CTC monitoring as an early response marker in metastatic breast cancer, said lead author Wolfgang Janni, MD, PhD, of the Ulm University Hospital, Ulm, Germany. He was speaking at an online press conference for the virtual San Antonio Breast Cancer Symposium (SABCS) 2020, where the new study will be presented this week.
The investigators say the findings from this meta-analysis add to literature in which “several studies suggest clinical utility” of measuring CTC levels as a means of assessing response status for patients with metastatic breast cancer.
Unfortunately, the new study does not show that assessing CTCs over time improves clinical outcomes, which is an ongoing problem in the literature, said Virginia Kaklamani, MD, University of Texas Health Sciences Center, San Antonio, Texas, who is also a meeting co-director.
“Previous randomized clinical trial data have shown that assessing CTCs does not benefit patients (vs not assessing),” Kaklamani told Medscape Medical News.
Kaklamani explained how CTC assessments have worked in practice. “You do these circulating tumor cell tests and you find, for example, that the number increases. The assumption is the treatment’s not working. So you switch treatments around,” she explained. That pattern can be repeated every 3 to 4 weeks, resulting in more toxicity, which, in turn, may nullify any treatment benefit.
However, she noted that, so far, key data have come from the era of chemotherapy and do not reflect targeted therapies, which may make a difference. In addition, the more recent ability to assess and identify circulating tumor DNA may allow clinicians to match drugs to mutations, which may have greater impact on cancer outcomes.
Currently, CTCs are best used by researchers, Kaklamani said during the press conference, because they have not been definitively proven to improve patient results.
Investigator Janni did not object to that description.
But in a press statement, he suggested that CTCs can be used currently by clinicians.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” Janni said in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued.”
But, to Kaklamani’s point, an article published in November in JAMA Oncology showed that use of CTCs did not yield significant clinical benefit in comparison with use of other clinical factors in determining whether to choose endocrine therapy or chemotherapy. In that randomized trial, which was conducted in Europe and included women with HR-positive, HER2-negative breast cancer, progression-free survival was similar in both arms, as reported by Medscape Medical News. However, use of chemotherapy (and attendant toxicity) was greater among women in the CTC arm, which was considered an undesirable outcome by experts not involved with the trial.
Details of the study results
For their study, Janni and colleagues conducted a comprehensive pooled analysis of globally available data. They identified 4079 metastatic breast cancer patients who had undergone baseline and follow-up CTC measurements (at least one, at a median of 29 days later) in previous clinical trials.
The investigators analyzed changes in CTC levels between baseline and follow-up to determine whether they were associated with OS.
Of the 2961 patients who were CTC-positive at baseline, 1855 remained CTC-positive after treatment was initiated (positive/positive), and 1106 patients had converted to CTC-negative status (positive/negative).
Of the 1118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), and 305 had become CTC-positive (negative/positive).
As noted above, median OS was greatest for patients who were negative/negative (47 months), followed by patients who were positive/negative (32.2 months), negative/positive (29.6 months), and positive/positive (17.8 months).
Hazard ratios in which the reference group was negative/negative were 1.52 for the positive/negative group, 1.74 for the negative/positive group, and 3.15 for the positive/positive group (P < .0001 for all groups).
These CTC dynamics were found across all breast cancer subtypes, said Janni.
“These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment,” said Janni in the press statement. “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”
The study was supported by Menarini Silicon Biosystems, the makers of CellSearch, the CTC test used for all of the patients and studies in the meta-analysis. Janni received a research grant from Menarini Silicon Biosystems. Other study authors have financial ties to healthcare industries. Kaklamani has received consulting fees from Amgen, Eisai, Puma, Celldex, AstraZeneca, and Athenex; fees for non-CME services received directly from commercial interest or their agents from Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, and Novartis; and has contracted research with Eisai.
This article first appeared on Medscape.com.
FROM SABCS 2020
Should CTCs guide treatment choice in HR+, HER2– breast cancer?
investigators wrote in JAMA Oncology.
However, authors of a related editorial suggested CTC counts are not adequate for guiding treatment choice in this population.
In a phase 3 trial, investigators compared the use of CTC counts and the use of clinical factors to guide the decision between chemotherapy and endocrine therapy. Results showed similar progression-free survival (PFS) and overall survival (OS) with both methods but more chemotherapy use with the CTC method.
“The results of this trial demonstrate the reliability and clinical utility of CTC count to guide the choice between single-agent endocrine therapy and chemotherapy as first-line treatment,” but “at the cost of a higher proportion of patients treated with chemotherapy,” study author François-Clement Bidard, MD, PhD, of Institut Curie in Saint-Cloud, France, and colleagues wrote.
The investigators explained that endocrine therapy is the preferred first-line treatment option in this patient population, but chemotherapy is used when women are in visceral crisis, with rapidly progressive, symptomatic disease. The decision usually rests on clinical factors, such as tumor subtype and performance status, but there’s interphysician variability.
The team hoped to find a “more reliable, standardized, and reproducible” biomarker to help remove some of the uncertainty from the situation. They tested CTC count, a well-established prognostic indicator of PFS and OS, as a candidate.
Study results
The trial included 755 patients with hormone receptor–positive, HER2-negative breast cancer in the per-protocol population. The patients’ median age was 63 years (range, 30-88 years).
Among the 377 patients randomized to the CTC arm, those with counts at or above 5 CTCs per 7.5 mL received chemotherapy, while those with a lower count received endocrine therapy.
The 378 patients in the standard-care group received endocrine therapy or chemotherapy based on provider choice guided by clinical factors.
Chemotherapy was given to 37% of patients in the CTC arm and 27% of those in the standard arm.
The median PFS was 15.5 months in the CTC arm and 13.9 months in the standard arm, which meant the primary endpoint of noninferiority was met (hazard ratio, 0.94; 90% confidence interval, 0.81-1.09).
Age older than 60 years was the only baseline characteristic associated with better PFS with CTC-driven decision-making. This may be because of the greater “use of endocrine therapy as the clinically favored treatment, whatever the other clinicopathologic characteristics,” in older subjects, the investigators wrote.
As with PFS, the median OS was similar between the study arms – 47.3 months in the CTC arm and 42.8 months in the standard arm (HR, 0.91; 95% CI, 0.71-1.16).
‘Not good enough’
The investigators behind this study had “a worthy goal,” according to authors of a related editorial.
Without “predictive biomarkers, we are left with our clinical knowledge, experience, and intuition. Patients are left with uncertainty, doubt, and fear,” Tarah Ballinger, MD,, of Indiana University, Indianapolis, and colleagues wrote in the editorial.
However, the editorialists had concerns about the findings. For one thing, the investigators hypothesized that relying on CTC would lead to a deescalation from chemotherapy to endocrine therapy, but use of chemotherapy was actually 10% higher in the CTC arm.
“Adding to or replacing the parameters we use to make a clinical decision should help us improve the lives of patients. ... We should demand an improvement in outcomes before accepting a strategy that exposes more patients to more toxic therapy. Not worse simply is not good enough,” the editorialists wrote.
In addition, the trial was completed before CDK4/6 inhibitors became a standard add-on with endocrine therapy for hormone receptor–positive, HER2-negative patients.
“The overall response rate to CDK4/6 inhibitor therapy is higher than with traditional chemotherapy, and several randomized trials have failed to show a survival benefit of upfront chemotherapy compared with CDK4/6 inhibitor use. ... Thus, it is even less likely that we can assume that baseline high CTC count corresponds to a need for chemotherapy in a modern treatment landscape that offers more patients more benefit from hormone therapy,” Dr. Ballinger and colleagues wrote.
The editorialists concluded that CTC count “alone at baseline primarily reflects disease bulk, much like anatomic staging, rather than disease biology. As treatments become more rooted in our knowledge of breast cancer biology, decisions based on disease bulk are decidedly out of place.”
Perhaps a better use, they suggested, is for treatment personalization. For instance, patients with persistently elevated CTCs despite standard approaches could consider trials of novel targeted therapies, or CTCs could be sequenced to identify actionable molecular targets, achieving a “clinical utility that merely counting CTCs lacks,” the editorialists wrote.
This study was funded by the Institut Curie, the French National Cancer Institute, and Menarini Silicon Biosystems, the maker of the CTC assay used in the trial. The investigators disclosed relationships with Menarini and many other companies. Dr. Ballinger receives honoraria from Medscape, which is owned by the same company as this news organization.
SOURCE: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.
investigators wrote in JAMA Oncology.
However, authors of a related editorial suggested CTC counts are not adequate for guiding treatment choice in this population.
In a phase 3 trial, investigators compared the use of CTC counts and the use of clinical factors to guide the decision between chemotherapy and endocrine therapy. Results showed similar progression-free survival (PFS) and overall survival (OS) with both methods but more chemotherapy use with the CTC method.
“The results of this trial demonstrate the reliability and clinical utility of CTC count to guide the choice between single-agent endocrine therapy and chemotherapy as first-line treatment,” but “at the cost of a higher proportion of patients treated with chemotherapy,” study author François-Clement Bidard, MD, PhD, of Institut Curie in Saint-Cloud, France, and colleagues wrote.
The investigators explained that endocrine therapy is the preferred first-line treatment option in this patient population, but chemotherapy is used when women are in visceral crisis, with rapidly progressive, symptomatic disease. The decision usually rests on clinical factors, such as tumor subtype and performance status, but there’s interphysician variability.
The team hoped to find a “more reliable, standardized, and reproducible” biomarker to help remove some of the uncertainty from the situation. They tested CTC count, a well-established prognostic indicator of PFS and OS, as a candidate.
Study results
The trial included 755 patients with hormone receptor–positive, HER2-negative breast cancer in the per-protocol population. The patients’ median age was 63 years (range, 30-88 years).
Among the 377 patients randomized to the CTC arm, those with counts at or above 5 CTCs per 7.5 mL received chemotherapy, while those with a lower count received endocrine therapy.
The 378 patients in the standard-care group received endocrine therapy or chemotherapy based on provider choice guided by clinical factors.
Chemotherapy was given to 37% of patients in the CTC arm and 27% of those in the standard arm.
The median PFS was 15.5 months in the CTC arm and 13.9 months in the standard arm, which meant the primary endpoint of noninferiority was met (hazard ratio, 0.94; 90% confidence interval, 0.81-1.09).
Age older than 60 years was the only baseline characteristic associated with better PFS with CTC-driven decision-making. This may be because of the greater “use of endocrine therapy as the clinically favored treatment, whatever the other clinicopathologic characteristics,” in older subjects, the investigators wrote.
As with PFS, the median OS was similar between the study arms – 47.3 months in the CTC arm and 42.8 months in the standard arm (HR, 0.91; 95% CI, 0.71-1.16).
‘Not good enough’
The investigators behind this study had “a worthy goal,” according to authors of a related editorial.
Without “predictive biomarkers, we are left with our clinical knowledge, experience, and intuition. Patients are left with uncertainty, doubt, and fear,” Tarah Ballinger, MD,, of Indiana University, Indianapolis, and colleagues wrote in the editorial.
However, the editorialists had concerns about the findings. For one thing, the investigators hypothesized that relying on CTC would lead to a deescalation from chemotherapy to endocrine therapy, but use of chemotherapy was actually 10% higher in the CTC arm.
“Adding to or replacing the parameters we use to make a clinical decision should help us improve the lives of patients. ... We should demand an improvement in outcomes before accepting a strategy that exposes more patients to more toxic therapy. Not worse simply is not good enough,” the editorialists wrote.
In addition, the trial was completed before CDK4/6 inhibitors became a standard add-on with endocrine therapy for hormone receptor–positive, HER2-negative patients.
“The overall response rate to CDK4/6 inhibitor therapy is higher than with traditional chemotherapy, and several randomized trials have failed to show a survival benefit of upfront chemotherapy compared with CDK4/6 inhibitor use. ... Thus, it is even less likely that we can assume that baseline high CTC count corresponds to a need for chemotherapy in a modern treatment landscape that offers more patients more benefit from hormone therapy,” Dr. Ballinger and colleagues wrote.
The editorialists concluded that CTC count “alone at baseline primarily reflects disease bulk, much like anatomic staging, rather than disease biology. As treatments become more rooted in our knowledge of breast cancer biology, decisions based on disease bulk are decidedly out of place.”
Perhaps a better use, they suggested, is for treatment personalization. For instance, patients with persistently elevated CTCs despite standard approaches could consider trials of novel targeted therapies, or CTCs could be sequenced to identify actionable molecular targets, achieving a “clinical utility that merely counting CTCs lacks,” the editorialists wrote.
This study was funded by the Institut Curie, the French National Cancer Institute, and Menarini Silicon Biosystems, the maker of the CTC assay used in the trial. The investigators disclosed relationships with Menarini and many other companies. Dr. Ballinger receives honoraria from Medscape, which is owned by the same company as this news organization.
SOURCE: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.
investigators wrote in JAMA Oncology.
However, authors of a related editorial suggested CTC counts are not adequate for guiding treatment choice in this population.
In a phase 3 trial, investigators compared the use of CTC counts and the use of clinical factors to guide the decision between chemotherapy and endocrine therapy. Results showed similar progression-free survival (PFS) and overall survival (OS) with both methods but more chemotherapy use with the CTC method.
“The results of this trial demonstrate the reliability and clinical utility of CTC count to guide the choice between single-agent endocrine therapy and chemotherapy as first-line treatment,” but “at the cost of a higher proportion of patients treated with chemotherapy,” study author François-Clement Bidard, MD, PhD, of Institut Curie in Saint-Cloud, France, and colleagues wrote.
The investigators explained that endocrine therapy is the preferred first-line treatment option in this patient population, but chemotherapy is used when women are in visceral crisis, with rapidly progressive, symptomatic disease. The decision usually rests on clinical factors, such as tumor subtype and performance status, but there’s interphysician variability.
The team hoped to find a “more reliable, standardized, and reproducible” biomarker to help remove some of the uncertainty from the situation. They tested CTC count, a well-established prognostic indicator of PFS and OS, as a candidate.
Study results
The trial included 755 patients with hormone receptor–positive, HER2-negative breast cancer in the per-protocol population. The patients’ median age was 63 years (range, 30-88 years).
Among the 377 patients randomized to the CTC arm, those with counts at or above 5 CTCs per 7.5 mL received chemotherapy, while those with a lower count received endocrine therapy.
The 378 patients in the standard-care group received endocrine therapy or chemotherapy based on provider choice guided by clinical factors.
Chemotherapy was given to 37% of patients in the CTC arm and 27% of those in the standard arm.
The median PFS was 15.5 months in the CTC arm and 13.9 months in the standard arm, which meant the primary endpoint of noninferiority was met (hazard ratio, 0.94; 90% confidence interval, 0.81-1.09).
Age older than 60 years was the only baseline characteristic associated with better PFS with CTC-driven decision-making. This may be because of the greater “use of endocrine therapy as the clinically favored treatment, whatever the other clinicopathologic characteristics,” in older subjects, the investigators wrote.
As with PFS, the median OS was similar between the study arms – 47.3 months in the CTC arm and 42.8 months in the standard arm (HR, 0.91; 95% CI, 0.71-1.16).
‘Not good enough’
The investigators behind this study had “a worthy goal,” according to authors of a related editorial.
Without “predictive biomarkers, we are left with our clinical knowledge, experience, and intuition. Patients are left with uncertainty, doubt, and fear,” Tarah Ballinger, MD,, of Indiana University, Indianapolis, and colleagues wrote in the editorial.
However, the editorialists had concerns about the findings. For one thing, the investigators hypothesized that relying on CTC would lead to a deescalation from chemotherapy to endocrine therapy, but use of chemotherapy was actually 10% higher in the CTC arm.
“Adding to or replacing the parameters we use to make a clinical decision should help us improve the lives of patients. ... We should demand an improvement in outcomes before accepting a strategy that exposes more patients to more toxic therapy. Not worse simply is not good enough,” the editorialists wrote.
In addition, the trial was completed before CDK4/6 inhibitors became a standard add-on with endocrine therapy for hormone receptor–positive, HER2-negative patients.
“The overall response rate to CDK4/6 inhibitor therapy is higher than with traditional chemotherapy, and several randomized trials have failed to show a survival benefit of upfront chemotherapy compared with CDK4/6 inhibitor use. ... Thus, it is even less likely that we can assume that baseline high CTC count corresponds to a need for chemotherapy in a modern treatment landscape that offers more patients more benefit from hormone therapy,” Dr. Ballinger and colleagues wrote.
The editorialists concluded that CTC count “alone at baseline primarily reflects disease bulk, much like anatomic staging, rather than disease biology. As treatments become more rooted in our knowledge of breast cancer biology, decisions based on disease bulk are decidedly out of place.”
Perhaps a better use, they suggested, is for treatment personalization. For instance, patients with persistently elevated CTCs despite standard approaches could consider trials of novel targeted therapies, or CTCs could be sequenced to identify actionable molecular targets, achieving a “clinical utility that merely counting CTCs lacks,” the editorialists wrote.
This study was funded by the Institut Curie, the French National Cancer Institute, and Menarini Silicon Biosystems, the maker of the CTC assay used in the trial. The investigators disclosed relationships with Menarini and many other companies. Dr. Ballinger receives honoraria from Medscape, which is owned by the same company as this news organization.
SOURCE: Bidard FC et al. JAMA Oncol. 2020 Nov 5. doi: 10.1001/jamaoncol.2020.5660.
FROM JAMA ONCOLOGY
Pembrolizumab approved for triple-negative breast cancer
The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) in combination with chemotherapy to treat locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1, as determined by a combined positive score of 10 or greater on an FDA-approved assay.
The FDA also approved a PD-L1 assay for selecting TNBC patients for pembrolizumab, the PD-L1 IHC 22C3 pharmDx.
Pembrolizumab is approved for numerous indications in the United States, but the new approval is its first breast cancer indication.
The accelerated approval for pembrolizumab in TNBC was based on progression-free survival (PFS) in the KEYNOTE-355 trial. The FDA noted that continued approval of pembrolizumab in TNBC “may be contingent upon verification and description of clinical benefit in the confirmatory trials.”
KEYNOTE-355 enrolled patients with locally recurrent unresectable or metastatic TNBC who had not received chemotherapy in the metastatic setting. Patients were randomized to chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) plus placebo (n = 281) or chemotherapy plus pembrolizumab at 200 mg on day 1 every 3 weeks (n = 562).
Among PD-L1-positive patients (n = 323), the median PFS was 5.6 months in the placebo arm and 9.7 months in the pembrolizumab arm (hazard ratio, 0.65; P = .0012).
The recommended pembrolizumab dose in TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Pembrolizumab can cause immune-mediated adverse reactions that may be severe or fatal, according to Merck, the manufacturer of pembrolizumab. These adverse reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplant.
“Based on the severity of the adverse reaction, [pembrolizumab] should be withheld or discontinued and corticosteroids administered if appropriate,” the company noted.
For more details on pembrolizumab, see the full prescribing information.
The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) in combination with chemotherapy to treat locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1, as determined by a combined positive score of 10 or greater on an FDA-approved assay.
The FDA also approved a PD-L1 assay for selecting TNBC patients for pembrolizumab, the PD-L1 IHC 22C3 pharmDx.
Pembrolizumab is approved for numerous indications in the United States, but the new approval is its first breast cancer indication.
The accelerated approval for pembrolizumab in TNBC was based on progression-free survival (PFS) in the KEYNOTE-355 trial. The FDA noted that continued approval of pembrolizumab in TNBC “may be contingent upon verification and description of clinical benefit in the confirmatory trials.”
KEYNOTE-355 enrolled patients with locally recurrent unresectable or metastatic TNBC who had not received chemotherapy in the metastatic setting. Patients were randomized to chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) plus placebo (n = 281) or chemotherapy plus pembrolizumab at 200 mg on day 1 every 3 weeks (n = 562).
Among PD-L1-positive patients (n = 323), the median PFS was 5.6 months in the placebo arm and 9.7 months in the pembrolizumab arm (hazard ratio, 0.65; P = .0012).
The recommended pembrolizumab dose in TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Pembrolizumab can cause immune-mediated adverse reactions that may be severe or fatal, according to Merck, the manufacturer of pembrolizumab. These adverse reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplant.
“Based on the severity of the adverse reaction, [pembrolizumab] should be withheld or discontinued and corticosteroids administered if appropriate,” the company noted.
For more details on pembrolizumab, see the full prescribing information.
The Food and Drug Administration has granted accelerated approval for pembrolizumab (Keytruda) in combination with chemotherapy to treat locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) that expresses PD-L1, as determined by a combined positive score of 10 or greater on an FDA-approved assay.
The FDA also approved a PD-L1 assay for selecting TNBC patients for pembrolizumab, the PD-L1 IHC 22C3 pharmDx.
Pembrolizumab is approved for numerous indications in the United States, but the new approval is its first breast cancer indication.
The accelerated approval for pembrolizumab in TNBC was based on progression-free survival (PFS) in the KEYNOTE-355 trial. The FDA noted that continued approval of pembrolizumab in TNBC “may be contingent upon verification and description of clinical benefit in the confirmatory trials.”
KEYNOTE-355 enrolled patients with locally recurrent unresectable or metastatic TNBC who had not received chemotherapy in the metastatic setting. Patients were randomized to chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin) plus placebo (n = 281) or chemotherapy plus pembrolizumab at 200 mg on day 1 every 3 weeks (n = 562).
Among PD-L1-positive patients (n = 323), the median PFS was 5.6 months in the placebo arm and 9.7 months in the pembrolizumab arm (hazard ratio, 0.65; P = .0012).
The recommended pembrolizumab dose in TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months.
Pembrolizumab can cause immune-mediated adverse reactions that may be severe or fatal, according to Merck, the manufacturer of pembrolizumab. These adverse reactions include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplant.
“Based on the severity of the adverse reaction, [pembrolizumab] should be withheld or discontinued and corticosteroids administered if appropriate,” the company noted.
For more details on pembrolizumab, see the full prescribing information.
FROM THE FOOD AND DRUG ADMINISTRATION
Divergent findings with paclitaxel and nab-paclitaxel in TNBC
The trials, IMpassion130 and IMpassion131, both enrolled patients with metastatic or unresectable, locally advanced TNBC.
In IMpassion131, adding atezolizumab to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS), regardless of programmed death–ligand 1 (PD-L1) expression.
In IMpassion130, adding atezolizumab to nab-paclitaxel did not improve OS in the intention-to-treat (ITT) population but did provide a “clinically meaningful” improvement in OS among PD-L1-positive patients, according to investigators.
IMpassion130 and IMpassion131 were presented during the same session at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
Potential reasons for the different outcomes in the two studies require further exploration, according to David Miles, MD, of Mount Vernon Cancer Centre in Northwood, England, who presented the findings from IMpassion131.
ESMO discussant Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill, posited three possible explanations for the divergent findings. The steroids necessary with paclitaxel dosing may have had a negative effect on immune checkpoint inhibitor activity, differences in study populations may have played a role, or the divergent findings could be caused by chance.
Steroid use in IMpassion131 could have played a negative role because of its lympholytic activity, but other indications with steroid use have not demonstrated attenuated benefits, said Leisha A. Emens, MD, PhD, of the University of Pittsburgh Medical Center, who presented the findings from IMpassion130 at ESMO 2020.
“If I were a patient, based on the data to date, I would want nab-paclitaxel with atezolizumab,” Dr. Emens said.
Trial details
Both trials are phase 3, double-blind, placebo-controlled studies of women with metastatic or unresectable locally advanced TNBC who had received no prior therapy for advanced TNBC.
IMpassion130 included 451 patients randomized to atezolizumab plus nab-paclitaxel and 451 randomized to placebo plus nab-paclitaxel. Patients received nab-paclitaxel at a starting dose of 100 mg/m2 via IV infusion on days 1, 8, and 15 of each 28-day cycle for at least six cycles.
In both studies, patients received atezolizumab at 840 mg on days 1 and 15 of a 28-day cycle in their active treatment arms.
IMpassion131 included 651 patients randomized 2:1 to atezolizumab plus paclitaxel (n = 431) or placebo plus paclitaxel (n = 220). Patients received paclitaxel at 90 mg/m2 on days 1, 8, and 15 every 28 days until disease progression or unacceptable toxicity.
Baseline characteristics were well balanced between the treatment arms in both studies. Less than half of patients – 45% in IMpassion131 and 41% in IMpassion130 – were PD-L1 positive.
Results of IMpassion131
The primary endpoint in IMpassion131 was PFS, and there was no significant difference in PFS between the treatment arms.
“The primary objective of IMpassion131 was not met,” Dr. Miles said. “[The] addition of atezolizumab to paclitaxel did not significantly improve PFS in patients with PD-L1-positive metastatic triple-negative breast cancer.”
In the PD-L1-positive population, the median PFS was 5.7 months in the placebo arm and 6.0 months in the atezolizumab arm (stratified hazard ratio, 0.82, P = .20).
In the ITT population, the median PFS was 5.6 months in the control arm and 5.7 months in the atezolizumab arm (HR, 0.86).
In subgroup analyses, Dr. Miles noted, “There was no clue about adverse or beneficial effects in any subgroup.”
The updated OS analysis demonstrated no benefit with atezolizumab in the ITT population or the PD-L1-positive population. In fact, there was a trend toward better OS for the control group in the latter analysis.
In the PD-L1-positive population, the median OS was 28.3 months in the control arm and 22.1 months in the atezolizumab arm (HR, 1.12). The 2-year OS rates were 51% and 49%, respectively.
In the ITT population, the median OS was 22.8 months in the control arm and 19.2 months in the atezolizumab arm (HR, 1.11). The 2-year OS rates were 45% and 42%, respectively.
The safety profile of the atezolizumab-paclitaxel combination was consistent with known side effects of the individual drugs, Dr. Miles said. There were four fatal treatment-related adverse events in the atezolizumab arm.
Results of IMpassion130
Presenting the final OS analysis from IMpassion130, Dr. Emens noted that the study’s findings have led to recommendations for atezolizumab plus nab-paclitaxel as first-line treatment of PD-L1-positive TNBC in international guidelines.
The median OS in the ITT population was 18.7 months in the placebo arm and 21.0 months in the atezolizumab arm (stratified HR, 0.87, P = .077). The 3-year OS rates were 25% and 28%, respectively.
The median OS in the PD-L1-positive population was 17.9 months in the placebo arm and 25.4 months in the atezolizumab arm (HR, 0.67). The 3-year OS rates were 22% and 36%, respectively.
A P value is not available for the between-arm OS comparison in the PD-L1-positive population. OS was not formally tested in this group because the OS boundary for statistical significance was not crossed in the ITT population. However, Dr. Emens said there was a “clinically meaningful” OS benefit observed with atezolizumab in the PD-L1-positive patients.
Treatment withdrawals caused by adverse events were more common in the atezolizumab arm (19% vs. 8%). The most common of these was neuropathy, Dr. Emens said. However, she noted that atezolizumab-related adverse events were generally low grade and easily managed.
“These results support a positive benefit-risk profile for atezolizumab plus nab-paclitaxel as first-line therapy in patients with PD-L1-positive metastatic triple-negative breast cancer,” Dr. Emens concluded.
Both studies were funded by F. Hoffman–La Roche. Dr. Miles, Dr. Emens, and Dr. Carey disclosed financial relationships with Roche and other companies.
SOURCES: Miles D et al. ESMO 2020, Abstract LBA15; Emens LA et al. ESMO 2020, Abstract LBA16.
The trials, IMpassion130 and IMpassion131, both enrolled patients with metastatic or unresectable, locally advanced TNBC.
In IMpassion131, adding atezolizumab to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS), regardless of programmed death–ligand 1 (PD-L1) expression.
In IMpassion130, adding atezolizumab to nab-paclitaxel did not improve OS in the intention-to-treat (ITT) population but did provide a “clinically meaningful” improvement in OS among PD-L1-positive patients, according to investigators.
IMpassion130 and IMpassion131 were presented during the same session at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
Potential reasons for the different outcomes in the two studies require further exploration, according to David Miles, MD, of Mount Vernon Cancer Centre in Northwood, England, who presented the findings from IMpassion131.
ESMO discussant Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill, posited three possible explanations for the divergent findings. The steroids necessary with paclitaxel dosing may have had a negative effect on immune checkpoint inhibitor activity, differences in study populations may have played a role, or the divergent findings could be caused by chance.
Steroid use in IMpassion131 could have played a negative role because of its lympholytic activity, but other indications with steroid use have not demonstrated attenuated benefits, said Leisha A. Emens, MD, PhD, of the University of Pittsburgh Medical Center, who presented the findings from IMpassion130 at ESMO 2020.
“If I were a patient, based on the data to date, I would want nab-paclitaxel with atezolizumab,” Dr. Emens said.
Trial details
Both trials are phase 3, double-blind, placebo-controlled studies of women with metastatic or unresectable locally advanced TNBC who had received no prior therapy for advanced TNBC.
IMpassion130 included 451 patients randomized to atezolizumab plus nab-paclitaxel and 451 randomized to placebo plus nab-paclitaxel. Patients received nab-paclitaxel at a starting dose of 100 mg/m2 via IV infusion on days 1, 8, and 15 of each 28-day cycle for at least six cycles.
In both studies, patients received atezolizumab at 840 mg on days 1 and 15 of a 28-day cycle in their active treatment arms.
IMpassion131 included 651 patients randomized 2:1 to atezolizumab plus paclitaxel (n = 431) or placebo plus paclitaxel (n = 220). Patients received paclitaxel at 90 mg/m2 on days 1, 8, and 15 every 28 days until disease progression or unacceptable toxicity.
Baseline characteristics were well balanced between the treatment arms in both studies. Less than half of patients – 45% in IMpassion131 and 41% in IMpassion130 – were PD-L1 positive.
Results of IMpassion131
The primary endpoint in IMpassion131 was PFS, and there was no significant difference in PFS between the treatment arms.
“The primary objective of IMpassion131 was not met,” Dr. Miles said. “[The] addition of atezolizumab to paclitaxel did not significantly improve PFS in patients with PD-L1-positive metastatic triple-negative breast cancer.”
In the PD-L1-positive population, the median PFS was 5.7 months in the placebo arm and 6.0 months in the atezolizumab arm (stratified hazard ratio, 0.82, P = .20).
In the ITT population, the median PFS was 5.6 months in the control arm and 5.7 months in the atezolizumab arm (HR, 0.86).
In subgroup analyses, Dr. Miles noted, “There was no clue about adverse or beneficial effects in any subgroup.”
The updated OS analysis demonstrated no benefit with atezolizumab in the ITT population or the PD-L1-positive population. In fact, there was a trend toward better OS for the control group in the latter analysis.
In the PD-L1-positive population, the median OS was 28.3 months in the control arm and 22.1 months in the atezolizumab arm (HR, 1.12). The 2-year OS rates were 51% and 49%, respectively.
In the ITT population, the median OS was 22.8 months in the control arm and 19.2 months in the atezolizumab arm (HR, 1.11). The 2-year OS rates were 45% and 42%, respectively.
The safety profile of the atezolizumab-paclitaxel combination was consistent with known side effects of the individual drugs, Dr. Miles said. There were four fatal treatment-related adverse events in the atezolizumab arm.
Results of IMpassion130
Presenting the final OS analysis from IMpassion130, Dr. Emens noted that the study’s findings have led to recommendations for atezolizumab plus nab-paclitaxel as first-line treatment of PD-L1-positive TNBC in international guidelines.
The median OS in the ITT population was 18.7 months in the placebo arm and 21.0 months in the atezolizumab arm (stratified HR, 0.87, P = .077). The 3-year OS rates were 25% and 28%, respectively.
The median OS in the PD-L1-positive population was 17.9 months in the placebo arm and 25.4 months in the atezolizumab arm (HR, 0.67). The 3-year OS rates were 22% and 36%, respectively.
A P value is not available for the between-arm OS comparison in the PD-L1-positive population. OS was not formally tested in this group because the OS boundary for statistical significance was not crossed in the ITT population. However, Dr. Emens said there was a “clinically meaningful” OS benefit observed with atezolizumab in the PD-L1-positive patients.
Treatment withdrawals caused by adverse events were more common in the atezolizumab arm (19% vs. 8%). The most common of these was neuropathy, Dr. Emens said. However, she noted that atezolizumab-related adverse events were generally low grade and easily managed.
“These results support a positive benefit-risk profile for atezolizumab plus nab-paclitaxel as first-line therapy in patients with PD-L1-positive metastatic triple-negative breast cancer,” Dr. Emens concluded.
Both studies were funded by F. Hoffman–La Roche. Dr. Miles, Dr. Emens, and Dr. Carey disclosed financial relationships with Roche and other companies.
SOURCES: Miles D et al. ESMO 2020, Abstract LBA15; Emens LA et al. ESMO 2020, Abstract LBA16.
The trials, IMpassion130 and IMpassion131, both enrolled patients with metastatic or unresectable, locally advanced TNBC.
In IMpassion131, adding atezolizumab to paclitaxel did not improve progression-free survival (PFS) or overall survival (OS), regardless of programmed death–ligand 1 (PD-L1) expression.
In IMpassion130, adding atezolizumab to nab-paclitaxel did not improve OS in the intention-to-treat (ITT) population but did provide a “clinically meaningful” improvement in OS among PD-L1-positive patients, according to investigators.
IMpassion130 and IMpassion131 were presented during the same session at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
Potential reasons for the different outcomes in the two studies require further exploration, according to David Miles, MD, of Mount Vernon Cancer Centre in Northwood, England, who presented the findings from IMpassion131.
ESMO discussant Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill, posited three possible explanations for the divergent findings. The steroids necessary with paclitaxel dosing may have had a negative effect on immune checkpoint inhibitor activity, differences in study populations may have played a role, or the divergent findings could be caused by chance.
Steroid use in IMpassion131 could have played a negative role because of its lympholytic activity, but other indications with steroid use have not demonstrated attenuated benefits, said Leisha A. Emens, MD, PhD, of the University of Pittsburgh Medical Center, who presented the findings from IMpassion130 at ESMO 2020.
“If I were a patient, based on the data to date, I would want nab-paclitaxel with atezolizumab,” Dr. Emens said.
Trial details
Both trials are phase 3, double-blind, placebo-controlled studies of women with metastatic or unresectable locally advanced TNBC who had received no prior therapy for advanced TNBC.
IMpassion130 included 451 patients randomized to atezolizumab plus nab-paclitaxel and 451 randomized to placebo plus nab-paclitaxel. Patients received nab-paclitaxel at a starting dose of 100 mg/m2 via IV infusion on days 1, 8, and 15 of each 28-day cycle for at least six cycles.
In both studies, patients received atezolizumab at 840 mg on days 1 and 15 of a 28-day cycle in their active treatment arms.
IMpassion131 included 651 patients randomized 2:1 to atezolizumab plus paclitaxel (n = 431) or placebo plus paclitaxel (n = 220). Patients received paclitaxel at 90 mg/m2 on days 1, 8, and 15 every 28 days until disease progression or unacceptable toxicity.
Baseline characteristics were well balanced between the treatment arms in both studies. Less than half of patients – 45% in IMpassion131 and 41% in IMpassion130 – were PD-L1 positive.
Results of IMpassion131
The primary endpoint in IMpassion131 was PFS, and there was no significant difference in PFS between the treatment arms.
“The primary objective of IMpassion131 was not met,” Dr. Miles said. “[The] addition of atezolizumab to paclitaxel did not significantly improve PFS in patients with PD-L1-positive metastatic triple-negative breast cancer.”
In the PD-L1-positive population, the median PFS was 5.7 months in the placebo arm and 6.0 months in the atezolizumab arm (stratified hazard ratio, 0.82, P = .20).
In the ITT population, the median PFS was 5.6 months in the control arm and 5.7 months in the atezolizumab arm (HR, 0.86).
In subgroup analyses, Dr. Miles noted, “There was no clue about adverse or beneficial effects in any subgroup.”
The updated OS analysis demonstrated no benefit with atezolizumab in the ITT population or the PD-L1-positive population. In fact, there was a trend toward better OS for the control group in the latter analysis.
In the PD-L1-positive population, the median OS was 28.3 months in the control arm and 22.1 months in the atezolizumab arm (HR, 1.12). The 2-year OS rates were 51% and 49%, respectively.
In the ITT population, the median OS was 22.8 months in the control arm and 19.2 months in the atezolizumab arm (HR, 1.11). The 2-year OS rates were 45% and 42%, respectively.
The safety profile of the atezolizumab-paclitaxel combination was consistent with known side effects of the individual drugs, Dr. Miles said. There were four fatal treatment-related adverse events in the atezolizumab arm.
Results of IMpassion130
Presenting the final OS analysis from IMpassion130, Dr. Emens noted that the study’s findings have led to recommendations for atezolizumab plus nab-paclitaxel as first-line treatment of PD-L1-positive TNBC in international guidelines.
The median OS in the ITT population was 18.7 months in the placebo arm and 21.0 months in the atezolizumab arm (stratified HR, 0.87, P = .077). The 3-year OS rates were 25% and 28%, respectively.
The median OS in the PD-L1-positive population was 17.9 months in the placebo arm and 25.4 months in the atezolizumab arm (HR, 0.67). The 3-year OS rates were 22% and 36%, respectively.
A P value is not available for the between-arm OS comparison in the PD-L1-positive population. OS was not formally tested in this group because the OS boundary for statistical significance was not crossed in the ITT population. However, Dr. Emens said there was a “clinically meaningful” OS benefit observed with atezolizumab in the PD-L1-positive patients.
Treatment withdrawals caused by adverse events were more common in the atezolizumab arm (19% vs. 8%). The most common of these was neuropathy, Dr. Emens said. However, she noted that atezolizumab-related adverse events were generally low grade and easily managed.
“These results support a positive benefit-risk profile for atezolizumab plus nab-paclitaxel as first-line therapy in patients with PD-L1-positive metastatic triple-negative breast cancer,” Dr. Emens concluded.
Both studies were funded by F. Hoffman–La Roche. Dr. Miles, Dr. Emens, and Dr. Carey disclosed financial relationships with Roche and other companies.
SOURCES: Miles D et al. ESMO 2020, Abstract LBA15; Emens LA et al. ESMO 2020, Abstract LBA16.
FROM ESMO 2020
First-in-class ADC ups survival in mTNBC
The first-in-class drug is directed at trophoblast cell surface antigen 2 (Trop-2), which is highly expressed in breast cancer. Research on the drug was presented at the European Society for Medical Oncology Virtual Congress 2020.
ASCENT randomly assigned more than 500 patients who had metastatic TNBC and who had experienced disease progression after a median of four lines of therapy to receive either SG or physician’s choice of chemotherapy. SG significantly improved median progression-free survival (5.6 vs 1.7 months; hazard ratio [HR], 0.41; P < .0001) and median overall survival (12.1 vs 6.7 months; HR, 0.48; P < .0001).
The response rate was 35% for SG vs 5% for chemotherapy (P < .0001).
The study was presented by Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital, Boston, Massachusetts.
He said that because the safety profile of SG is consistent with previous reports and the treatment discontinuation rate was low, the clinical benefit “confirms the use of sacituzumab govitecan” in metastatic TNBC. This was a reference to the fact that the drug previously received accelerated approval on the basis of early data.
Bardia added that ongoing studies are evaluating the use of SG in earlier lines of therapy, including neoadjuvant settings in combination with other targeted agents, as well as in hormone receptor–positive metastatic breast cancer. One such study is the phase 3 TROPiCS-02 study, which is actively accruing patients.
Invited discussant Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal, said the treatment algorithm for the management of TNBC will need to be updated in light of these results.
“In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of therapy,” she said.
She noted that the study design raised some questions over the way such trials should be conducted and the future sequencing of treatments.
Objections to study design and execution
Discussant Cardoso said the choice of progression-free survival as the primary endpoint for the trial was not ideal.
“In the metastatic setting, and particularly for triple-negative breast cancer, where the median survival is quite low and where each line of treatment, particularly after the second line, has a short duration, the primary endpoint should have been overall survival,” she commented.
“Luckily, we saw some results, but we could have missed it,” Cardoso said. She made “a plea to make sure that overall survival is at least the co–primary endpoint” in the future.
Cardoso also said it was not clear to her why the trial had to be stopped. “For the current patients, if there is no crossover, there is no benefit in stopping the trial,” she said.
She went on: “For future patients, it’s better to have the final results sufficiently powered.” She noted that the benefit seen in ASCENT was “moderate” and “so not a substantial breakthrough.” She added that it was “important not to stop trials too early.”
On the positive side, Cardoso said the median number of previous lines of therapy was “quite remarkable for this subtype, and it is important then for us to discuss sequencing,” particularly given that so many patients received checkpoint inhibitors before entering the trial.
Safety and a focus on diarrhea
Investigator Bardia explained that SG is an antibody-drug conjugate directed at Trop-2, which is highly expressed in breast cancer.
The antibody is linked to SN-38, the active metabolite of irinotecan, via a hydrolyzable linker that makes internalization and enzymatic cleavage by tumor cells unnecessary.
Hydrolysis of the linker releases SN-38 both within the tumor cell and extracellularly to induce a so-called bystander effect, in which neighboring tumors cells may be killed even if they do not express Trop-2.
On the basis of positive results from phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with metastatic TNBC who experience disease progression after at least two prior therapies.
ASCENT was therefore a phase 3 confirmatory study. Patients with metastatic TNBC who had received at least two prior chemotherapy regimens were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or to receive physician’s choice of treatment.
Physicians could choose eribulin, vinorelbine, gemcitabine, or capecitabine.
The patients continued receiving treatment until disease progression or unacceptable toxicity occurred. On the unanimous recommendation of the data safety monitoring committee, the trial was ended early because of “compelling evidence of efficacy.”
In all, 267 patients were randomly assigned to receive SG. Of those patients, 15 remain on treatment. Treatment was discontinued for 199 patients who experienced disease progression. In the control arm, 262 patients were included, none of whom are still on treatment; 166 discontinued because of disease progression.
The current analysis is limited to 235 patients in the SG group and, in the control arm, 233 patients who did not have brain metastases. Patients with brain metastases will be the subject of a later analysis.
All but one patient in both treatment groups were women. The median age was approximately 54 years. The median number of prior treatment regimens was four. All patients had previously received chemotherapy, and between 26% and 29% have taken checkpoint inhibitors.
By the data cutoff of March 11, 2020, patients had received a median of seven treatment cycles with SG. Progression-free survival was adjudicated by blind, independent central review. The median duration of response was of borderline significance, at 6.3 months vs 3.6 months (P = .057).
Bardia showed that the results were consistent among all subgroups, including subgroups determined on the basis of age, number of prior therapies, whether patients had received prior immune checkpoint therapy, and the presence of liver metastases.
With respect to safety, the important grade 3 or higher treatment-related adverse events were neutropenia (seen in 51% of SG patients vs 33% of patients in the control arm), diarrhea (10% vs <1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).
Despite the fact that the adverse event rate was higher with SG than with physician’s choice of chemotherapy, the percentage of such events that led to treatment discontinuation was numerically lower, at 4.7% vs 5.4%.
Cardoso highlighted the “substantial percentage” of patients with diarrhea and nausea in the trial and noted that “all grades” of these adverse events “affect quality of life.”
The focus therefore should be on patient education, prophylaxis, and “the early management of side effects,” she said.
This point was taken up in the postpresentation debate. Bardia said the high rate of diarrhea “likely relates to the toxic payload, which is SN-38, which is known to cause diarrhea.
“Loperamide or immodium prophylaxis can be used in patients who receive this drug, and in general, our experience with the use of sacituzumab govitecan is you can control the diarrhea,” Bardia said.
He added: “There is also a different side effect that occurs during the infusion of SG, which is abdominal cramping and diarrhea, and that’s more of a cholinergic reaction. For that, atropine is the best medication to use.”
The study was funded by Immunomedics Inc. Bardia has disclosed financial ties with Immunomedics and multiple other pharmaceutical companies. Cardoso has disclosed financial ties to multiple drug companies.
This article first appeared on Medscape.com.
The first-in-class drug is directed at trophoblast cell surface antigen 2 (Trop-2), which is highly expressed in breast cancer. Research on the drug was presented at the European Society for Medical Oncology Virtual Congress 2020.
ASCENT randomly assigned more than 500 patients who had metastatic TNBC and who had experienced disease progression after a median of four lines of therapy to receive either SG or physician’s choice of chemotherapy. SG significantly improved median progression-free survival (5.6 vs 1.7 months; hazard ratio [HR], 0.41; P < .0001) and median overall survival (12.1 vs 6.7 months; HR, 0.48; P < .0001).
The response rate was 35% for SG vs 5% for chemotherapy (P < .0001).
The study was presented by Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital, Boston, Massachusetts.
He said that because the safety profile of SG is consistent with previous reports and the treatment discontinuation rate was low, the clinical benefit “confirms the use of sacituzumab govitecan” in metastatic TNBC. This was a reference to the fact that the drug previously received accelerated approval on the basis of early data.
Bardia added that ongoing studies are evaluating the use of SG in earlier lines of therapy, including neoadjuvant settings in combination with other targeted agents, as well as in hormone receptor–positive metastatic breast cancer. One such study is the phase 3 TROPiCS-02 study, which is actively accruing patients.
Invited discussant Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal, said the treatment algorithm for the management of TNBC will need to be updated in light of these results.
“In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of therapy,” she said.
She noted that the study design raised some questions over the way such trials should be conducted and the future sequencing of treatments.
Objections to study design and execution
Discussant Cardoso said the choice of progression-free survival as the primary endpoint for the trial was not ideal.
“In the metastatic setting, and particularly for triple-negative breast cancer, where the median survival is quite low and where each line of treatment, particularly after the second line, has a short duration, the primary endpoint should have been overall survival,” she commented.
“Luckily, we saw some results, but we could have missed it,” Cardoso said. She made “a plea to make sure that overall survival is at least the co–primary endpoint” in the future.
Cardoso also said it was not clear to her why the trial had to be stopped. “For the current patients, if there is no crossover, there is no benefit in stopping the trial,” she said.
She went on: “For future patients, it’s better to have the final results sufficiently powered.” She noted that the benefit seen in ASCENT was “moderate” and “so not a substantial breakthrough.” She added that it was “important not to stop trials too early.”
On the positive side, Cardoso said the median number of previous lines of therapy was “quite remarkable for this subtype, and it is important then for us to discuss sequencing,” particularly given that so many patients received checkpoint inhibitors before entering the trial.
Safety and a focus on diarrhea
Investigator Bardia explained that SG is an antibody-drug conjugate directed at Trop-2, which is highly expressed in breast cancer.
The antibody is linked to SN-38, the active metabolite of irinotecan, via a hydrolyzable linker that makes internalization and enzymatic cleavage by tumor cells unnecessary.
Hydrolysis of the linker releases SN-38 both within the tumor cell and extracellularly to induce a so-called bystander effect, in which neighboring tumors cells may be killed even if they do not express Trop-2.
On the basis of positive results from phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with metastatic TNBC who experience disease progression after at least two prior therapies.
ASCENT was therefore a phase 3 confirmatory study. Patients with metastatic TNBC who had received at least two prior chemotherapy regimens were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or to receive physician’s choice of treatment.
Physicians could choose eribulin, vinorelbine, gemcitabine, or capecitabine.
The patients continued receiving treatment until disease progression or unacceptable toxicity occurred. On the unanimous recommendation of the data safety monitoring committee, the trial was ended early because of “compelling evidence of efficacy.”
In all, 267 patients were randomly assigned to receive SG. Of those patients, 15 remain on treatment. Treatment was discontinued for 199 patients who experienced disease progression. In the control arm, 262 patients were included, none of whom are still on treatment; 166 discontinued because of disease progression.
The current analysis is limited to 235 patients in the SG group and, in the control arm, 233 patients who did not have brain metastases. Patients with brain metastases will be the subject of a later analysis.
All but one patient in both treatment groups were women. The median age was approximately 54 years. The median number of prior treatment regimens was four. All patients had previously received chemotherapy, and between 26% and 29% have taken checkpoint inhibitors.
By the data cutoff of March 11, 2020, patients had received a median of seven treatment cycles with SG. Progression-free survival was adjudicated by blind, independent central review. The median duration of response was of borderline significance, at 6.3 months vs 3.6 months (P = .057).
Bardia showed that the results were consistent among all subgroups, including subgroups determined on the basis of age, number of prior therapies, whether patients had received prior immune checkpoint therapy, and the presence of liver metastases.
With respect to safety, the important grade 3 or higher treatment-related adverse events were neutropenia (seen in 51% of SG patients vs 33% of patients in the control arm), diarrhea (10% vs <1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).
Despite the fact that the adverse event rate was higher with SG than with physician’s choice of chemotherapy, the percentage of such events that led to treatment discontinuation was numerically lower, at 4.7% vs 5.4%.
Cardoso highlighted the “substantial percentage” of patients with diarrhea and nausea in the trial and noted that “all grades” of these adverse events “affect quality of life.”
The focus therefore should be on patient education, prophylaxis, and “the early management of side effects,” she said.
This point was taken up in the postpresentation debate. Bardia said the high rate of diarrhea “likely relates to the toxic payload, which is SN-38, which is known to cause diarrhea.
“Loperamide or immodium prophylaxis can be used in patients who receive this drug, and in general, our experience with the use of sacituzumab govitecan is you can control the diarrhea,” Bardia said.
He added: “There is also a different side effect that occurs during the infusion of SG, which is abdominal cramping and diarrhea, and that’s more of a cholinergic reaction. For that, atropine is the best medication to use.”
The study was funded by Immunomedics Inc. Bardia has disclosed financial ties with Immunomedics and multiple other pharmaceutical companies. Cardoso has disclosed financial ties to multiple drug companies.
This article first appeared on Medscape.com.
The first-in-class drug is directed at trophoblast cell surface antigen 2 (Trop-2), which is highly expressed in breast cancer. Research on the drug was presented at the European Society for Medical Oncology Virtual Congress 2020.
ASCENT randomly assigned more than 500 patients who had metastatic TNBC and who had experienced disease progression after a median of four lines of therapy to receive either SG or physician’s choice of chemotherapy. SG significantly improved median progression-free survival (5.6 vs 1.7 months; hazard ratio [HR], 0.41; P < .0001) and median overall survival (12.1 vs 6.7 months; HR, 0.48; P < .0001).
The response rate was 35% for SG vs 5% for chemotherapy (P < .0001).
The study was presented by Aditya Bardia, MD, MPH, a medical oncologist at Massachusetts General Hospital, Boston, Massachusetts.
He said that because the safety profile of SG is consistent with previous reports and the treatment discontinuation rate was low, the clinical benefit “confirms the use of sacituzumab govitecan” in metastatic TNBC. This was a reference to the fact that the drug previously received accelerated approval on the basis of early data.
Bardia added that ongoing studies are evaluating the use of SG in earlier lines of therapy, including neoadjuvant settings in combination with other targeted agents, as well as in hormone receptor–positive metastatic breast cancer. One such study is the phase 3 TROPiCS-02 study, which is actively accruing patients.
Invited discussant Fatima Cardoso, MD, director of the Breast Unit at Champalimaud Clinical Center, Lisbon, Portugal, said the treatment algorithm for the management of TNBC will need to be updated in light of these results.
“In my opinion, we should now add sacituzumab govitecan as a new treatment option for patients treated with two or more lines of therapy,” she said.
She noted that the study design raised some questions over the way such trials should be conducted and the future sequencing of treatments.
Objections to study design and execution
Discussant Cardoso said the choice of progression-free survival as the primary endpoint for the trial was not ideal.
“In the metastatic setting, and particularly for triple-negative breast cancer, where the median survival is quite low and where each line of treatment, particularly after the second line, has a short duration, the primary endpoint should have been overall survival,” she commented.
“Luckily, we saw some results, but we could have missed it,” Cardoso said. She made “a plea to make sure that overall survival is at least the co–primary endpoint” in the future.
Cardoso also said it was not clear to her why the trial had to be stopped. “For the current patients, if there is no crossover, there is no benefit in stopping the trial,” she said.
She went on: “For future patients, it’s better to have the final results sufficiently powered.” She noted that the benefit seen in ASCENT was “moderate” and “so not a substantial breakthrough.” She added that it was “important not to stop trials too early.”
On the positive side, Cardoso said the median number of previous lines of therapy was “quite remarkable for this subtype, and it is important then for us to discuss sequencing,” particularly given that so many patients received checkpoint inhibitors before entering the trial.
Safety and a focus on diarrhea
Investigator Bardia explained that SG is an antibody-drug conjugate directed at Trop-2, which is highly expressed in breast cancer.
The antibody is linked to SN-38, the active metabolite of irinotecan, via a hydrolyzable linker that makes internalization and enzymatic cleavage by tumor cells unnecessary.
Hydrolysis of the linker releases SN-38 both within the tumor cell and extracellularly to induce a so-called bystander effect, in which neighboring tumors cells may be killed even if they do not express Trop-2.
On the basis of positive results from phase 1/2 trial data, SG was granted accelerated approval by the US Food and Drug Administration for patients with metastatic TNBC who experience disease progression after at least two prior therapies.
ASCENT was therefore a phase 3 confirmatory study. Patients with metastatic TNBC who had received at least two prior chemotherapy regimens were randomly assigned in a 1:1 ratio to receive intravenous SG on days 1 and 8 of a 21-day cycle or to receive physician’s choice of treatment.
Physicians could choose eribulin, vinorelbine, gemcitabine, or capecitabine.
The patients continued receiving treatment until disease progression or unacceptable toxicity occurred. On the unanimous recommendation of the data safety monitoring committee, the trial was ended early because of “compelling evidence of efficacy.”
In all, 267 patients were randomly assigned to receive SG. Of those patients, 15 remain on treatment. Treatment was discontinued for 199 patients who experienced disease progression. In the control arm, 262 patients were included, none of whom are still on treatment; 166 discontinued because of disease progression.
The current analysis is limited to 235 patients in the SG group and, in the control arm, 233 patients who did not have brain metastases. Patients with brain metastases will be the subject of a later analysis.
All but one patient in both treatment groups were women. The median age was approximately 54 years. The median number of prior treatment regimens was four. All patients had previously received chemotherapy, and between 26% and 29% have taken checkpoint inhibitors.
By the data cutoff of March 11, 2020, patients had received a median of seven treatment cycles with SG. Progression-free survival was adjudicated by blind, independent central review. The median duration of response was of borderline significance, at 6.3 months vs 3.6 months (P = .057).
Bardia showed that the results were consistent among all subgroups, including subgroups determined on the basis of age, number of prior therapies, whether patients had received prior immune checkpoint therapy, and the presence of liver metastases.
With respect to safety, the important grade 3 or higher treatment-related adverse events were neutropenia (seen in 51% of SG patients vs 33% of patients in the control arm), diarrhea (10% vs <1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).
Despite the fact that the adverse event rate was higher with SG than with physician’s choice of chemotherapy, the percentage of such events that led to treatment discontinuation was numerically lower, at 4.7% vs 5.4%.
Cardoso highlighted the “substantial percentage” of patients with diarrhea and nausea in the trial and noted that “all grades” of these adverse events “affect quality of life.”
The focus therefore should be on patient education, prophylaxis, and “the early management of side effects,” she said.
This point was taken up in the postpresentation debate. Bardia said the high rate of diarrhea “likely relates to the toxic payload, which is SN-38, which is known to cause diarrhea.
“Loperamide or immodium prophylaxis can be used in patients who receive this drug, and in general, our experience with the use of sacituzumab govitecan is you can control the diarrhea,” Bardia said.
He added: “There is also a different side effect that occurs during the infusion of SG, which is abdominal cramping and diarrhea, and that’s more of a cholinergic reaction. For that, atropine is the best medication to use.”
The study was funded by Immunomedics Inc. Bardia has disclosed financial ties with Immunomedics and multiple other pharmaceutical companies. Cardoso has disclosed financial ties to multiple drug companies.
This article first appeared on Medscape.com.
FROM ESMO 2020
Survey quantifies COVID-19’s impact on oncology
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.
The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).
Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.
The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.
The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.
The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.
The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).
The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
Impact on treatment
The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).
Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).
Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.
On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.
Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.
“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.
“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.
Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.
Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.
Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
Telehealth, meetings, and trials
The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).
Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).
While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.
Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.
Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.
He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”
This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.
SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.
FROM ESMO 2020
Atezolizumab TNBC indication ‘in jeopardy’ because of phase 3 results
The FDA said the phase 3 IMpassion131 trial showed that atezolizumab plus paclitaxel did not significantly reduce the risk of cancer progression and death, when compared with paclitaxel plus placebo, in programmed death-ligand 1 (PD-L1)–positive patients.
“Additionally, interim overall survival results favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1-positive population and total population,” the FDA noted.
As a result, “health care professionals should not replace paclitaxel protein-bound (Abraxane) with paclitaxel in clinical practice,” the FDA advised.
Atezolizumab is approved for use in combination with protein-bound paclitaxel, also known as nanoparticle albumin–bound paclitaxel (nab-paclitaxel), to treat patients with unresectable, locally advanced, or metastatic TNBC whose tumors express PD-L1, as detected by an FDA-approved test. The combination was granted accelerated approval for this indication last year.
Atezolizumab plus nab-paclitaxel is the combination most often used in PD-L1-positive TNBC, as opposed to atezolizumab and unbound paclitaxel, said Melinda L. Telli, MD, an associate professor of medicine and director of the Stanford Cancer Institute Breast Cancer Program at Stanford (Calif.) University.
However, as the FDA noted, “continued approval of atezolizumab in combination with [nab-paclitaxel] may be contingent on proven benefit of the treatment in additional trials.”
Dr. Telli explained that atezolizumab was granted accelerated approval for the treatment of PD-L1-positive TNBC based on results of the phase 3 IMpassion130 trial, which compared nab-paclitaxel plus atezolizumab with nab-paclitaxel plus placebo.
“Additional data from IMpassion131 was hoped to be used to support the conversion of the accelerated approval to a full approval. Since IMpassion131 was negative, it unfortunately places the status of atezolizumab in [TNBC] in jeopardy as the benefits were not corroborated. The FDA may move to revoke the approval of atezolizumab for [TNBC],” Dr. Telli said.
In its alert, the FDA stated that it “will review the findings of IMpassion131 and will communicate new information regarding the IMpassion131 results and any potential changes to prescribing information.”
“We need to wait for full presentation and publication of the study results, but, in my assessment, the negative results in IMpassion131 are most likely due to differences in patient selection [from IMpassion130],” Dr. Telli said.
Results from IMpassion131 are scheduled to be presented at the ESMO Virtual Congress 2020.
The IMpassion trials were funded by Roche, maker of atezolizumab. Dr. Telli disclosed relationships with AbbVie, AstraZeneca, Merck, PharmaMar, Pfizer, and Tesaro.
The FDA said the phase 3 IMpassion131 trial showed that atezolizumab plus paclitaxel did not significantly reduce the risk of cancer progression and death, when compared with paclitaxel plus placebo, in programmed death-ligand 1 (PD-L1)–positive patients.
“Additionally, interim overall survival results favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1-positive population and total population,” the FDA noted.
As a result, “health care professionals should not replace paclitaxel protein-bound (Abraxane) with paclitaxel in clinical practice,” the FDA advised.
Atezolizumab is approved for use in combination with protein-bound paclitaxel, also known as nanoparticle albumin–bound paclitaxel (nab-paclitaxel), to treat patients with unresectable, locally advanced, or metastatic TNBC whose tumors express PD-L1, as detected by an FDA-approved test. The combination was granted accelerated approval for this indication last year.
Atezolizumab plus nab-paclitaxel is the combination most often used in PD-L1-positive TNBC, as opposed to atezolizumab and unbound paclitaxel, said Melinda L. Telli, MD, an associate professor of medicine and director of the Stanford Cancer Institute Breast Cancer Program at Stanford (Calif.) University.
However, as the FDA noted, “continued approval of atezolizumab in combination with [nab-paclitaxel] may be contingent on proven benefit of the treatment in additional trials.”
Dr. Telli explained that atezolizumab was granted accelerated approval for the treatment of PD-L1-positive TNBC based on results of the phase 3 IMpassion130 trial, which compared nab-paclitaxel plus atezolizumab with nab-paclitaxel plus placebo.
“Additional data from IMpassion131 was hoped to be used to support the conversion of the accelerated approval to a full approval. Since IMpassion131 was negative, it unfortunately places the status of atezolizumab in [TNBC] in jeopardy as the benefits were not corroborated. The FDA may move to revoke the approval of atezolizumab for [TNBC],” Dr. Telli said.
In its alert, the FDA stated that it “will review the findings of IMpassion131 and will communicate new information regarding the IMpassion131 results and any potential changes to prescribing information.”
“We need to wait for full presentation and publication of the study results, but, in my assessment, the negative results in IMpassion131 are most likely due to differences in patient selection [from IMpassion130],” Dr. Telli said.
Results from IMpassion131 are scheduled to be presented at the ESMO Virtual Congress 2020.
The IMpassion trials were funded by Roche, maker of atezolizumab. Dr. Telli disclosed relationships with AbbVie, AstraZeneca, Merck, PharmaMar, Pfizer, and Tesaro.
The FDA said the phase 3 IMpassion131 trial showed that atezolizumab plus paclitaxel did not significantly reduce the risk of cancer progression and death, when compared with paclitaxel plus placebo, in programmed death-ligand 1 (PD-L1)–positive patients.
“Additionally, interim overall survival results favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1-positive population and total population,” the FDA noted.
As a result, “health care professionals should not replace paclitaxel protein-bound (Abraxane) with paclitaxel in clinical practice,” the FDA advised.
Atezolizumab is approved for use in combination with protein-bound paclitaxel, also known as nanoparticle albumin–bound paclitaxel (nab-paclitaxel), to treat patients with unresectable, locally advanced, or metastatic TNBC whose tumors express PD-L1, as detected by an FDA-approved test. The combination was granted accelerated approval for this indication last year.
Atezolizumab plus nab-paclitaxel is the combination most often used in PD-L1-positive TNBC, as opposed to atezolizumab and unbound paclitaxel, said Melinda L. Telli, MD, an associate professor of medicine and director of the Stanford Cancer Institute Breast Cancer Program at Stanford (Calif.) University.
However, as the FDA noted, “continued approval of atezolizumab in combination with [nab-paclitaxel] may be contingent on proven benefit of the treatment in additional trials.”
Dr. Telli explained that atezolizumab was granted accelerated approval for the treatment of PD-L1-positive TNBC based on results of the phase 3 IMpassion130 trial, which compared nab-paclitaxel plus atezolizumab with nab-paclitaxel plus placebo.
“Additional data from IMpassion131 was hoped to be used to support the conversion of the accelerated approval to a full approval. Since IMpassion131 was negative, it unfortunately places the status of atezolizumab in [TNBC] in jeopardy as the benefits were not corroborated. The FDA may move to revoke the approval of atezolizumab for [TNBC],” Dr. Telli said.
In its alert, the FDA stated that it “will review the findings of IMpassion131 and will communicate new information regarding the IMpassion131 results and any potential changes to prescribing information.”
“We need to wait for full presentation and publication of the study results, but, in my assessment, the negative results in IMpassion131 are most likely due to differences in patient selection [from IMpassion130],” Dr. Telli said.
Results from IMpassion131 are scheduled to be presented at the ESMO Virtual Congress 2020.
The IMpassion trials were funded by Roche, maker of atezolizumab. Dr. Telli disclosed relationships with AbbVie, AstraZeneca, Merck, PharmaMar, Pfizer, and Tesaro.