User login
RT of lymph nodes as good as dissection for the long-term
SAN ANTONIO – Both axillary radiation therapy and axillary lymph node dissection provide excellent, comparable locoregional control in patients with early-stage breast cancer who have a positive sentinel node, according to updated results of the European Organisation for Research and Treatment of Cancer’s AMAROS trial.
The 10-year cumulative incidence rate of axillary recurrence was 1.82% with radiation and 0.93% with lymph node dissection, a nonsignificant difference (hazard ratio, 1.71; P = .365). Distant metastasis–free survival and overall survival also were statistically on par. The findings reinforce the trial’s 5-year results, which additionally showed a markedly lower incidence of lymphedema with axillary radiation therapy. Lead investigator Emiel J. T. Rutgers, MD, PhD, reflected on hesitation in the uptake of axillary radiation therapy among oncologists and discussed the AMAROS results in the context of the ACOSOG Z11 trial. Dr. Rutgers, the principal investigator of the AMAROS trial and a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, also described how the trial’s findings have altered practice at his institution.
Dr. Rutgers disclosed that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.
SAN ANTONIO – Both axillary radiation therapy and axillary lymph node dissection provide excellent, comparable locoregional control in patients with early-stage breast cancer who have a positive sentinel node, according to updated results of the European Organisation for Research and Treatment of Cancer’s AMAROS trial.
The 10-year cumulative incidence rate of axillary recurrence was 1.82% with radiation and 0.93% with lymph node dissection, a nonsignificant difference (hazard ratio, 1.71; P = .365). Distant metastasis–free survival and overall survival also were statistically on par. The findings reinforce the trial’s 5-year results, which additionally showed a markedly lower incidence of lymphedema with axillary radiation therapy. Lead investigator Emiel J. T. Rutgers, MD, PhD, reflected on hesitation in the uptake of axillary radiation therapy among oncologists and discussed the AMAROS results in the context of the ACOSOG Z11 trial. Dr. Rutgers, the principal investigator of the AMAROS trial and a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, also described how the trial’s findings have altered practice at his institution.
Dr. Rutgers disclosed that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.
SAN ANTONIO – Both axillary radiation therapy and axillary lymph node dissection provide excellent, comparable locoregional control in patients with early-stage breast cancer who have a positive sentinel node, according to updated results of the European Organisation for Research and Treatment of Cancer’s AMAROS trial.
The 10-year cumulative incidence rate of axillary recurrence was 1.82% with radiation and 0.93% with lymph node dissection, a nonsignificant difference (hazard ratio, 1.71; P = .365). Distant metastasis–free survival and overall survival also were statistically on par. The findings reinforce the trial’s 5-year results, which additionally showed a markedly lower incidence of lymphedema with axillary radiation therapy. Lead investigator Emiel J. T. Rutgers, MD, PhD, reflected on hesitation in the uptake of axillary radiation therapy among oncologists and discussed the AMAROS results in the context of the ACOSOG Z11 trial. Dr. Rutgers, the principal investigator of the AMAROS trial and a surgical oncologist at the Netherlands Cancer Institute in Amsterdam, also described how the trial’s findings have altered practice at his institution.
Dr. Rutgers disclosed that he had no relevant conflicts of interest. The study was supported by the EORTC Charitable Trust.
REPORTING FROM SABCS 2018
Nothing to gain from chemo after pCR achieved
SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may have little to gain from subsequent adjuvant chemotherapy except toxicity, according to a patient-level meta-analysis of more than 27,000 women. The analysis, reported by lead investigator Laura M. Spring, MD, at the San Antonio Breast Cancer Symposium, confirmed that, compared with residual disease, pCR was associated with significantly reduced risks of event-free survival events (hazard ratio, 0.31) and death (HR, 0.22). Moreover, the EFS benefit of a pCR was similar whether women went on to receive adjuvant chemotherapy (HR, 0.36) or not (HR, 0.36) (P = .60 for difference). Dr. Spring discussed overall and subgroup findings, implications for use of neoadjuvant chemotherapy, and how these new data may inform escalation and de-escalation of adjuvant therapy.
Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may have little to gain from subsequent adjuvant chemotherapy except toxicity, according to a patient-level meta-analysis of more than 27,000 women. The analysis, reported by lead investigator Laura M. Spring, MD, at the San Antonio Breast Cancer Symposium, confirmed that, compared with residual disease, pCR was associated with significantly reduced risks of event-free survival events (hazard ratio, 0.31) and death (HR, 0.22). Moreover, the EFS benefit of a pCR was similar whether women went on to receive adjuvant chemotherapy (HR, 0.36) or not (HR, 0.36) (P = .60 for difference). Dr. Spring discussed overall and subgroup findings, implications for use of neoadjuvant chemotherapy, and how these new data may inform escalation and de-escalation of adjuvant therapy.
Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
SAN ANTONIO – Women with localized breast cancer who achieve a pathological complete response (pCR) after neoadjuvant chemotherapy may have little to gain from subsequent adjuvant chemotherapy except toxicity, according to a patient-level meta-analysis of more than 27,000 women. The analysis, reported by lead investigator Laura M. Spring, MD, at the San Antonio Breast Cancer Symposium, confirmed that, compared with residual disease, pCR was associated with significantly reduced risks of event-free survival events (hazard ratio, 0.31) and death (HR, 0.22). Moreover, the EFS benefit of a pCR was similar whether women went on to receive adjuvant chemotherapy (HR, 0.36) or not (HR, 0.36) (P = .60 for difference). Dr. Spring discussed overall and subgroup findings, implications for use of neoadjuvant chemotherapy, and how these new data may inform escalation and de-escalation of adjuvant therapy.
Dr. Spring disclosed that she has a consulting or advisory role with Novartis and that she receives institutional research funding from Tesaro. The study was supported by grants from the National Cancer Institute and Susan G. Komen.
REPORTING FROM SABCS 2018
Small absolute difference between partial and whole breast irradiation
SAN ANTONIO – A phase 3 randomized NRG Oncology trial (NSABP B-39/RTOG 0413) was unable to rule out the possibility that, after lumpectomy, partial breast irradiation is inferior to whole breast irradiation when it comes to the ipsilateral breast tumor recurrences (invasive disease or ductal carcinoma in situ), reported Frank Vicini, MD, of MHP Radiation Oncology Institute, Pontiac, Mich.
The hazard ratio for this event with the former versus latter modality was 1.22, with the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5). However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was just 0.7% (4.6% vs. 3.9%). In a video interview, Dr. Vicini discussed whether this difference is clinically important, and the implications of the trial’s findings, taken together, for offering partial breast irradiation to patients.
Dr. Vicini disclosed that he is a research adviser for ImpediMed. The study was sponsored by the National Cancer Institute.
SAN ANTONIO – A phase 3 randomized NRG Oncology trial (NSABP B-39/RTOG 0413) was unable to rule out the possibility that, after lumpectomy, partial breast irradiation is inferior to whole breast irradiation when it comes to the ipsilateral breast tumor recurrences (invasive disease or ductal carcinoma in situ), reported Frank Vicini, MD, of MHP Radiation Oncology Institute, Pontiac, Mich.
The hazard ratio for this event with the former versus latter modality was 1.22, with the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5). However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was just 0.7% (4.6% vs. 3.9%). In a video interview, Dr. Vicini discussed whether this difference is clinically important, and the implications of the trial’s findings, taken together, for offering partial breast irradiation to patients.
Dr. Vicini disclosed that he is a research adviser for ImpediMed. The study was sponsored by the National Cancer Institute.
SAN ANTONIO – A phase 3 randomized NRG Oncology trial (NSABP B-39/RTOG 0413) was unable to rule out the possibility that, after lumpectomy, partial breast irradiation is inferior to whole breast irradiation when it comes to the ipsilateral breast tumor recurrences (invasive disease or ductal carcinoma in situ), reported Frank Vicini, MD, of MHP Radiation Oncology Institute, Pontiac, Mich.
The hazard ratio for this event with the former versus latter modality was 1.22, with the 90% confidence interval (0.94-1.58) falling just outside the predefined range to declare the two modalities equivalent (0.667-1.5). However, the absolute difference in the 10-year cumulative incidence of ipsilateral breast tumor recurrences was just 0.7% (4.6% vs. 3.9%). In a video interview, Dr. Vicini discussed whether this difference is clinically important, and the implications of the trial’s findings, taken together, for offering partial breast irradiation to patients.
Dr. Vicini disclosed that he is a research adviser for ImpediMed. The study was sponsored by the National Cancer Institute.
REPORTING FROM SABCS 2018
Adjuvant capecitabine found disappointing in TNBC
SAN ANTONIO – Adjuvant capecitabine does not improve outcomes in women with early-stage triple-negative breast cancer (TNBC) who have undergone resection and received standard chemotherapy, finds a phase 3, randomized, controlled trial jointly conducted by the Spanish GEICAM group and the Central and South American CIBOMA group. But the story may not end there.
Findings reported in a session and press conference at the San Antonio Breast Cancer Symposium showed that, compared with observation, eight cycles of adjuvant capecitabine (Xeloda) reduced the 5-year risks of disease-free survival events and death by a nonsignificant relative 18% and 8%, respectively, among all 876 women randomized. However, the subgroup whose tumors had the nonbasal phenotype saw large significant benefits, with 47% and 58% relative reductions in these risks, respectively.
“The trial is formally negative,” commented lead investigator Miguel Martín, MD, PhD, head of the medical oncology service at Hospital Gregorio Marañón in Madrid. However, the observation arm fared better than expected. In addition, the trial had a very low–risk patient population, which may help explain why its findings differ somewhat from the more positive findings of the similar CREATE-X trial.
“Our data don’t speak against the CREATE-X study. My personal view is that capecitabine is useful for some TNBC patients,” Dr. Martin said. “Our study is not finished because we are going to look at the genomic characteristics of this group defined as non–basal-like because we want to know more about this subgroup. We are planning also to reproduce our subset in the CREATE-X trial to see if this is a real finding because we are in the era of personalized medicine.”
TNBC is a broad group defined only by negative findings for the main markers having available treatments, he elaborated. “So if we could define a subpopulation that actually benefited from capecitabine, this will be great for the patients.” Currently, conventional pathology does not routinely report on tumor basal phenotype, so all TNBC patients receive the same drugs. “This is a mistake. We should select the right drug for the right patient. Probably not all breast cancer patients are sensitive to the same drugs. But the fact is that we don’t have funding to run trials looking at that because this kind of trial is not interesting for pharma companies.”
“That’s an important message that triple-negative is really a big, very heterogeneous group,” agreed SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of oncology programs at the University of Texas, Dallas.
Patients and clinicians alike are largely unaware of the presence of TNBC basal and nonbasal subtypes and their potential importance, he said. “We all need some education on that, us included. It’s a very, very heterogeneous group, it is one that is very challenging. We need to start by educating all of us that there is a need to do research on that. ... We have a duty to define this phenotype better.”
Study details
“TNBC is sensitive to chemotherapy, but a significant proportion of patients will eventually relapse after conventional anthracycline and taxane combinations, so we need new approaches to this population,” Dr. Martín noted.
The trial, joint GEICAM/2003-11 and CIBOMA/2004-01, was designed in 2004. Although no information about capecitabine in breast cancer was available at the time, the investigators selected this drug because it is non–cross-resistant with anthracyclines and taxanes.
About 55% of the patients randomized had node-negative disease and roughly 80% received adjuvant chemotherapy alone because neoadjuvant chemotherapy was generally not used 14 years ago, Dr. Martín noted.
After a median follow-up of 7.34 years, the 5-year disease-free survival rate—the trial’s primary endpoint—was 79.6% with capecitabine and 76.8% with observation, a nonsignificant difference in both unadjusted analysis (hazard ratio, 0.82; P = .136) and adjusted analysis (HR, 0.79; P = .082). The 5-year overall survival rate was 86.2% with capecitabine and 85.9% with observation, another nonsignificant difference (HR, 0.92; P = .623).
However, in subgroup analyses among the 248 patients with nonbasal disease, defined as immunohistochemically negative for both EGFR and CK5/6, capecitabine conferred a significant disease-free survival advantage (HR, 0.53; P = .02) and overall survival advantage (HR, 0.420; P = .007) relative to observation.
Interaction of basal/nonbasal phenotype with treatment was marginal for disease-free survival (P = .0694) and significant for overall survival (P = .0052).
In the nonbasal subgroup, the disease-free survival benefit of capecitabine was mainly driven by a reduction in distant recurrences, particularly in the liver and the brain.
Adjuvant capecitabine had tolerability that was “exactly as expected,” according to Dr. Martín. The median dose intensity was 86.3%, and 75.2% of patients completed all of the planned eight cycles.
The trial was supported by Roche, which also provided capecitabine. Dr. Martín reported receiving speaker’s honoraria from Pfizer and Eli Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Eli Lilly; and research grants from Novartis and Roche.
SOURCE: Martín M et al. SABCS 2018, Abstract GS2-04.
SAN ANTONIO – Adjuvant capecitabine does not improve outcomes in women with early-stage triple-negative breast cancer (TNBC) who have undergone resection and received standard chemotherapy, finds a phase 3, randomized, controlled trial jointly conducted by the Spanish GEICAM group and the Central and South American CIBOMA group. But the story may not end there.
Findings reported in a session and press conference at the San Antonio Breast Cancer Symposium showed that, compared with observation, eight cycles of adjuvant capecitabine (Xeloda) reduced the 5-year risks of disease-free survival events and death by a nonsignificant relative 18% and 8%, respectively, among all 876 women randomized. However, the subgroup whose tumors had the nonbasal phenotype saw large significant benefits, with 47% and 58% relative reductions in these risks, respectively.
“The trial is formally negative,” commented lead investigator Miguel Martín, MD, PhD, head of the medical oncology service at Hospital Gregorio Marañón in Madrid. However, the observation arm fared better than expected. In addition, the trial had a very low–risk patient population, which may help explain why its findings differ somewhat from the more positive findings of the similar CREATE-X trial.
“Our data don’t speak against the CREATE-X study. My personal view is that capecitabine is useful for some TNBC patients,” Dr. Martin said. “Our study is not finished because we are going to look at the genomic characteristics of this group defined as non–basal-like because we want to know more about this subgroup. We are planning also to reproduce our subset in the CREATE-X trial to see if this is a real finding because we are in the era of personalized medicine.”
TNBC is a broad group defined only by negative findings for the main markers having available treatments, he elaborated. “So if we could define a subpopulation that actually benefited from capecitabine, this will be great for the patients.” Currently, conventional pathology does not routinely report on tumor basal phenotype, so all TNBC patients receive the same drugs. “This is a mistake. We should select the right drug for the right patient. Probably not all breast cancer patients are sensitive to the same drugs. But the fact is that we don’t have funding to run trials looking at that because this kind of trial is not interesting for pharma companies.”
“That’s an important message that triple-negative is really a big, very heterogeneous group,” agreed SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of oncology programs at the University of Texas, Dallas.
Patients and clinicians alike are largely unaware of the presence of TNBC basal and nonbasal subtypes and their potential importance, he said. “We all need some education on that, us included. It’s a very, very heterogeneous group, it is one that is very challenging. We need to start by educating all of us that there is a need to do research on that. ... We have a duty to define this phenotype better.”
Study details
“TNBC is sensitive to chemotherapy, but a significant proportion of patients will eventually relapse after conventional anthracycline and taxane combinations, so we need new approaches to this population,” Dr. Martín noted.
The trial, joint GEICAM/2003-11 and CIBOMA/2004-01, was designed in 2004. Although no information about capecitabine in breast cancer was available at the time, the investigators selected this drug because it is non–cross-resistant with anthracyclines and taxanes.
About 55% of the patients randomized had node-negative disease and roughly 80% received adjuvant chemotherapy alone because neoadjuvant chemotherapy was generally not used 14 years ago, Dr. Martín noted.
After a median follow-up of 7.34 years, the 5-year disease-free survival rate—the trial’s primary endpoint—was 79.6% with capecitabine and 76.8% with observation, a nonsignificant difference in both unadjusted analysis (hazard ratio, 0.82; P = .136) and adjusted analysis (HR, 0.79; P = .082). The 5-year overall survival rate was 86.2% with capecitabine and 85.9% with observation, another nonsignificant difference (HR, 0.92; P = .623).
However, in subgroup analyses among the 248 patients with nonbasal disease, defined as immunohistochemically negative for both EGFR and CK5/6, capecitabine conferred a significant disease-free survival advantage (HR, 0.53; P = .02) and overall survival advantage (HR, 0.420; P = .007) relative to observation.
Interaction of basal/nonbasal phenotype with treatment was marginal for disease-free survival (P = .0694) and significant for overall survival (P = .0052).
In the nonbasal subgroup, the disease-free survival benefit of capecitabine was mainly driven by a reduction in distant recurrences, particularly in the liver and the brain.
Adjuvant capecitabine had tolerability that was “exactly as expected,” according to Dr. Martín. The median dose intensity was 86.3%, and 75.2% of patients completed all of the planned eight cycles.
The trial was supported by Roche, which also provided capecitabine. Dr. Martín reported receiving speaker’s honoraria from Pfizer and Eli Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Eli Lilly; and research grants from Novartis and Roche.
SOURCE: Martín M et al. SABCS 2018, Abstract GS2-04.
SAN ANTONIO – Adjuvant capecitabine does not improve outcomes in women with early-stage triple-negative breast cancer (TNBC) who have undergone resection and received standard chemotherapy, finds a phase 3, randomized, controlled trial jointly conducted by the Spanish GEICAM group and the Central and South American CIBOMA group. But the story may not end there.
Findings reported in a session and press conference at the San Antonio Breast Cancer Symposium showed that, compared with observation, eight cycles of adjuvant capecitabine (Xeloda) reduced the 5-year risks of disease-free survival events and death by a nonsignificant relative 18% and 8%, respectively, among all 876 women randomized. However, the subgroup whose tumors had the nonbasal phenotype saw large significant benefits, with 47% and 58% relative reductions in these risks, respectively.
“The trial is formally negative,” commented lead investigator Miguel Martín, MD, PhD, head of the medical oncology service at Hospital Gregorio Marañón in Madrid. However, the observation arm fared better than expected. In addition, the trial had a very low–risk patient population, which may help explain why its findings differ somewhat from the more positive findings of the similar CREATE-X trial.
“Our data don’t speak against the CREATE-X study. My personal view is that capecitabine is useful for some TNBC patients,” Dr. Martin said. “Our study is not finished because we are going to look at the genomic characteristics of this group defined as non–basal-like because we want to know more about this subgroup. We are planning also to reproduce our subset in the CREATE-X trial to see if this is a real finding because we are in the era of personalized medicine.”
TNBC is a broad group defined only by negative findings for the main markers having available treatments, he elaborated. “So if we could define a subpopulation that actually benefited from capecitabine, this will be great for the patients.” Currently, conventional pathology does not routinely report on tumor basal phenotype, so all TNBC patients receive the same drugs. “This is a mistake. We should select the right drug for the right patient. Probably not all breast cancer patients are sensitive to the same drugs. But the fact is that we don’t have funding to run trials looking at that because this kind of trial is not interesting for pharma companies.”
“That’s an important message that triple-negative is really a big, very heterogeneous group,” agreed SABCS codirector and press conference moderator Carlos Arteaga, MD, director of the Harold C. Simmons Comprehensive Cancer Center and associate dean of oncology programs at the University of Texas, Dallas.
Patients and clinicians alike are largely unaware of the presence of TNBC basal and nonbasal subtypes and their potential importance, he said. “We all need some education on that, us included. It’s a very, very heterogeneous group, it is one that is very challenging. We need to start by educating all of us that there is a need to do research on that. ... We have a duty to define this phenotype better.”
Study details
“TNBC is sensitive to chemotherapy, but a significant proportion of patients will eventually relapse after conventional anthracycline and taxane combinations, so we need new approaches to this population,” Dr. Martín noted.
The trial, joint GEICAM/2003-11 and CIBOMA/2004-01, was designed in 2004. Although no information about capecitabine in breast cancer was available at the time, the investigators selected this drug because it is non–cross-resistant with anthracyclines and taxanes.
About 55% of the patients randomized had node-negative disease and roughly 80% received adjuvant chemotherapy alone because neoadjuvant chemotherapy was generally not used 14 years ago, Dr. Martín noted.
After a median follow-up of 7.34 years, the 5-year disease-free survival rate—the trial’s primary endpoint—was 79.6% with capecitabine and 76.8% with observation, a nonsignificant difference in both unadjusted analysis (hazard ratio, 0.82; P = .136) and adjusted analysis (HR, 0.79; P = .082). The 5-year overall survival rate was 86.2% with capecitabine and 85.9% with observation, another nonsignificant difference (HR, 0.92; P = .623).
However, in subgroup analyses among the 248 patients with nonbasal disease, defined as immunohistochemically negative for both EGFR and CK5/6, capecitabine conferred a significant disease-free survival advantage (HR, 0.53; P = .02) and overall survival advantage (HR, 0.420; P = .007) relative to observation.
Interaction of basal/nonbasal phenotype with treatment was marginal for disease-free survival (P = .0694) and significant for overall survival (P = .0052).
In the nonbasal subgroup, the disease-free survival benefit of capecitabine was mainly driven by a reduction in distant recurrences, particularly in the liver and the brain.
Adjuvant capecitabine had tolerability that was “exactly as expected,” according to Dr. Martín. The median dose intensity was 86.3%, and 75.2% of patients completed all of the planned eight cycles.
The trial was supported by Roche, which also provided capecitabine. Dr. Martín reported receiving speaker’s honoraria from Pfizer and Eli Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Eli Lilly; and research grants from Novartis and Roche.
SOURCE: Martín M et al. SABCS 2018, Abstract GS2-04.
REPORTING FROM SABCS 2018
Key clinical point: Adjuvant capecitabine fails to improve outcomes in early-stage triple-negative breast cancer treated with surgery and standard chemotherapy.
Major finding: The 5-year disease-free survival rate was 79.6% with eight cycles of adjuvant capecitabine versus 76.8% with observation (adjusted hazard ratio, 0.79; P = .082).
Study details: A phase 3, randomized, controlled trial among 876 women with early-stage triple-negative breast cancer who had undergone surgery and received standard chemotherapy (joint GEICAM/2003-11 and CIBOMA/2004-01 trial).
Disclosures: The trial was supported by Roche, which also provided capecitabine. Dr. Martín reported receiving speaker’s honoraria from Pfizer and Eli Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Eli Lilly; and research grants from Novartis and Roche.
Source: Martín M et al. SABCS 2018, Abstract GS2-04.
Trio of biosimilars have good showing
Biosimilars for three widely used oncology drugs showed efficacy and safety in lung cancer and breast cancer similar to those of the reference products, according to findings reported at the 2018 annual meeting of the American Society of Clinical Oncology in Chicago.
Oncology biosimilars for bevacizumab (Avastin), trastuzumab (Herceptin), and filgrastim (Neupogen and others) have yielded positive results in various patient populations and clinical settings, investigators reported at the annual ASCO meeting. The findings advance the promise of new agents that have no clinically meaningful differences in efficacy and safety when compared with their reference drugs but have substantially lower cost.
“Biosimilars are here,” said Michael A Thompson, MD, PhD, of Aurora Health Care in Milwaukee, Wisconsin, “[although] issues remain, including clinical decision support and pathway adoption, naming differences across the world, competition and lower prices versus the illusion of a free market, and adoption to decrease costs and increase value to our patients.” Dr Thompson was commenting during an invited discussion at the meeting. He is the medical director of the Early Phase Cancer Research Program and the Oncology Precision Medicine Program at Aurora Health (also see Commentary at end of article).
Bevacizumab biosimilar
The REFLECTIONS trial (NCT02364999) was a multinational, first-line, randomized, controlled trial among 719 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients were randomized to paclitaxel and carboplatin chemotherapy plus either bevacizumab (sourced from the European Union) or the candidate bevacizumab biosimilar PF-06439535 on a double-blind basis, followed by monotherapy with the same assigned agent.
The overall response rate by week 19, confirmed by week 25 – the trial’s primary endpoint – was 45.3% with the biosimilar and 44.6% with bevacizumab, reported lead author Mark A Socinski, MD, executive medical director of the Florida Hospital Cancer Institute in Orlando. The confidence interval (CI) for the risk difference fell within the equivalence margins set by European Union regulators (-13% and +13% for the 95% CI). And the confidence interval for the risk ratio fell within the equivalence margins set by the US Food and Drug Administration (0.73 and 1.37 for the 90% CI) and Japanese regulators (0.729 and 1.371 for the 95% CI).
Median progression-free survival (PFS) was 9.0 months with the biosimilar and 7.7 months with bevacizumab (hazard ratio [HR], 0.974; P = .814), and corresponding 1-year rates were 30.8% and 29.3%, respectively, Dr Socinski reported. Median overall survival was 18.4 months and 17.8 months (HR, 1.001; P = .991), and corresponding 1-year rates were 66.4% and 68.8%.
Rates of grade 3 or higher hypertension, cardiac disorders, and bleeding did not differ significantly with the 2 agents. Patients also had similar rates of grade 3 or higher serious adverse events (AEs) and of fatal (grade 5) serious AEs with the biosimilar and bevacizumab (5.3% and 5.9%, respectively).
“Similarity between PF-06439535 and bevacizumab-EU was demonstrated for the primary efficacy endpoint of overall response rate. ... There were no clinically meaningful differences in safety profile shown in this trial, and similar pharmacokinetic and immunogenicity results were seen across treatment groups,” Dr Socinski summarized. “These results confirm the similarity demonstrated in earlier analytical, nonclinical, and clinical studies of PF-06439535 with bevacizumab-EU.”
Funding Pfizer sponsored the REFLECTIONS trial. Disclosures Dr Socinski disclosed that his institution receives research funding from Pfizer. Source Socinski MA et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. ASCO 2018, Abstract 109. https://meetinglibrary.asco.org/record/161702/abstract. Clinical trial registry number NCT02364999 https://clinicaltrials.gov/ct2/show/NCT02364999
Trastuzumab biosimilar
The phase 3 HERITAGE trial was a first-line, randomized, controlled trial that compared biosimilar trastuzumab-dkst (Ogivri) with trastuzumab in combination with taxane chemotherapy and then as maintenance monotherapy in 458 patients with HER2+ advanced breast cancer. The 24-week results, previously reported (JAMA. 2017 Jan 3;317[1]:37-47), showed a similar overall response rate with each agent when combined with chemotherapy. Rates of various AEs were essentially the same.
The 48-week results showed a median PFS of 11.1 months with trastuzumab-dkst and 11.1 months with trastuzumab (HR, 0.95; P = .842), reported senior investigator Hope S Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “The overall survival is immature but is impressive at over 80% at 52 weeks,” she noted.
Presence of overall response at 24 weeks correlated with duration of PFS at 48 weeks (biserial r = .752). “Additional patients achieved a response during the monotherapy portion of the treatment, which is intriguing and clearly emphasizes the importance of monotherapy, as well as the importance of having alternate agents at lower cost available,” Dr Rugo commented.
Common AEs through week 48 were much the same as those seen at week 24, with few additional [events] occurring during monotherapy. “No new safety issues were observed, and in fact, toxicity during monotherapy was quite minor,” she noted. “One thing that’s interesting here is that there was more arthralgia during the first 24 weeks with trastuzumab-dkst than with trastuzumab, but in monotherapy, this fell to a very low number and was identical between the 2 arms. Paclitaxel, which people stayed on for longer [with the biosimilar], may have been the cause of this.”
The 48-week rates of AEs of special interest – respiratory events, cardiac disorders, and infusion-related AEs – and of serious AEs were similar for the 2 agents.
“We didn’t see any additional serious cardiac events during monotherapy,” Dr Rugo noted. Mean and median left ventricular ejection fraction over 48 weeks were similar, as was the rate of LVEF, which dropped below 50% (4.0% with trastuzumab-dkst and 3.3% with trastuzumab). The incidences of antidrug antibody and neutralizing antibody were also comparably low in both groups.
“HERITAGE data, now at week 48, supports trastuzumab-dkst as a biosimilar to trastuzumab in all approved indications,” Dr Rugo said. “Final overall survival will be assessed after 36 months or after 240 deaths, whichever occurs first. Based on current data, this is predicted to conclude by the end of 2018, with final overall survival data available next year.”
Dr Rugo emphasized that trastuzumab-dkst provides “an additional high-quality treatment option for patients with HER2+ breast cancers in any setting. This study shows that biosimilars offer the potential for worldwide cost savings and improved access to life-saving therapies. It’s sobering to think that the patients enrolled in this study would not otherwise have had access to continued trastuzumab therapy, and so many of them are still alive with longer follow-up.”
Funding Mylan sponsored the HERITAGE trial. Disclosures Dr Rugo disclosed that she receives travel, accommodations, and/or expenses from Mylan. Source Manikhas A et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial. ASCO 2018, Abstract 110. https://meetinglibrary.asco.org/record/161572/abstract. Clinical trial registry number NCT02472964 https://clinicaltrials.gov/ct2/show/NCT02472964
Filgrastim biosimilar
Investigators led by Nadia Harbeck, MD, PhD, head of the Breast Center and chair for Conservative Oncology in the department of OB&GYN at the University of Munich (Germany), compared efficacy of filgrastim-sndz (Zarxio), a biosimilar of filgrastim (recombinant granulocyte colony-stimulating factor, or G-CSF), in a trial population with that of a real-world population of women receiving chemotherapy for breast cancer.
Data for the former came from PIONEER, a phase 3, randomized, controlled trial among patients with nonmetastatic breast cancer undergoing docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy in the neoadjuvant or adjuvant setting (Ann Oncol. 2015;26[9]:1948-53). Data for the latter came from MONITOR-GCSF, a postmarketing, open-label, observational cohort study among patients from 12 European countries receiving chemotherapy for various solid and hematologic malignancies (Support Care Cancer. 2016;24[2]:911-25).
Dr Harbeck and her colleagues compared 217 women who had nonmetastatic breast cancer from the trial with 466 women who had any-stage breast cancer (42% metastatic) from the real-world cohort.
Results showed that the 6.2% rate of chemotherapy-induced febrile neutropenia in any cycle seen in the real-world population was much the same as the 5.1% rate seen previously in the trial/biosimilar population. Findings were similar for temperature exceeding 38.5°C in any cycle: 3.4% and 5.6%, respectively. The real-world population had a lower rate of severe neutropenia than did the trial population (19.5% and 74.3%) and higher rates of infection (15.5% and 7.9%) and hospitalization caused by febrile neutropenia (3.9% and 1.8%). Findings were essentially the same in cycle-level analyses.
The real-world cohort had many fewer any-severity safety events of special interest than did the trial cohort, such as musculoskeletal/connective tissue disorders (20 and 261 events, respectively) and skin/subcutaneous tissue disorders (5 and 258 events). “Seeing these data, you have to keep in mind that the patients received totally different chemotherapy. TAC chemotherapy has a lot of chemotherapy-associated side effects,” Dr Harbeck noted. “The other thing is that MONITOR was a real-world database, and one could assume that there is some underreporting of events that are not directly correlated to the events that are of particular interest.”
Additional results available only from the trial showed that no patients developed binding or neutralizing antibodies against G-CSF.
“From a clinician’s point of view, it is very reassuring that we did not see any other safety signals in the real-world data than we saw in the randomized controlled trial and the efficacy was very, very similar,” Dr Harbeck commented. “Having seen the discrepancies in the data, I think it’s important to have randomized controlled trials to assess and monitor AEs for registration purposes and real-world evidence to reflect the daily clinical routine,” she concluded.
Funding Sandoz sponsored the PIONEER and MONITOR-GCSF trials. Disclosures Dr Harbeck disclosed that she has a consulting or advisory role with Sandoz. Source Harbeck N et al. Comparison of efficacy and safety of biosimilar filgrastim in a RCT (PIONEER) and real-world practice (MONITOR-GCSF). ASCO 2018, Abstract 111. https://meetinglibrary.asco.org/record/161688/abstract. Clinical trial registry number NCT01519700 https://clinicaltrials.gov/ct2/show/NCT01519700
Biosimilars for three widely used oncology drugs showed efficacy and safety in lung cancer and breast cancer similar to those of the reference products, according to findings reported at the 2018 annual meeting of the American Society of Clinical Oncology in Chicago.
Oncology biosimilars for bevacizumab (Avastin), trastuzumab (Herceptin), and filgrastim (Neupogen and others) have yielded positive results in various patient populations and clinical settings, investigators reported at the annual ASCO meeting. The findings advance the promise of new agents that have no clinically meaningful differences in efficacy and safety when compared with their reference drugs but have substantially lower cost.
“Biosimilars are here,” said Michael A Thompson, MD, PhD, of Aurora Health Care in Milwaukee, Wisconsin, “[although] issues remain, including clinical decision support and pathway adoption, naming differences across the world, competition and lower prices versus the illusion of a free market, and adoption to decrease costs and increase value to our patients.” Dr Thompson was commenting during an invited discussion at the meeting. He is the medical director of the Early Phase Cancer Research Program and the Oncology Precision Medicine Program at Aurora Health (also see Commentary at end of article).
Bevacizumab biosimilar
The REFLECTIONS trial (NCT02364999) was a multinational, first-line, randomized, controlled trial among 719 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients were randomized to paclitaxel and carboplatin chemotherapy plus either bevacizumab (sourced from the European Union) or the candidate bevacizumab biosimilar PF-06439535 on a double-blind basis, followed by monotherapy with the same assigned agent.
The overall response rate by week 19, confirmed by week 25 – the trial’s primary endpoint – was 45.3% with the biosimilar and 44.6% with bevacizumab, reported lead author Mark A Socinski, MD, executive medical director of the Florida Hospital Cancer Institute in Orlando. The confidence interval (CI) for the risk difference fell within the equivalence margins set by European Union regulators (-13% and +13% for the 95% CI). And the confidence interval for the risk ratio fell within the equivalence margins set by the US Food and Drug Administration (0.73 and 1.37 for the 90% CI) and Japanese regulators (0.729 and 1.371 for the 95% CI).
Median progression-free survival (PFS) was 9.0 months with the biosimilar and 7.7 months with bevacizumab (hazard ratio [HR], 0.974; P = .814), and corresponding 1-year rates were 30.8% and 29.3%, respectively, Dr Socinski reported. Median overall survival was 18.4 months and 17.8 months (HR, 1.001; P = .991), and corresponding 1-year rates were 66.4% and 68.8%.
Rates of grade 3 or higher hypertension, cardiac disorders, and bleeding did not differ significantly with the 2 agents. Patients also had similar rates of grade 3 or higher serious adverse events (AEs) and of fatal (grade 5) serious AEs with the biosimilar and bevacizumab (5.3% and 5.9%, respectively).
“Similarity between PF-06439535 and bevacizumab-EU was demonstrated for the primary efficacy endpoint of overall response rate. ... There were no clinically meaningful differences in safety profile shown in this trial, and similar pharmacokinetic and immunogenicity results were seen across treatment groups,” Dr Socinski summarized. “These results confirm the similarity demonstrated in earlier analytical, nonclinical, and clinical studies of PF-06439535 with bevacizumab-EU.”
Funding Pfizer sponsored the REFLECTIONS trial. Disclosures Dr Socinski disclosed that his institution receives research funding from Pfizer. Source Socinski MA et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. ASCO 2018, Abstract 109. https://meetinglibrary.asco.org/record/161702/abstract. Clinical trial registry number NCT02364999 https://clinicaltrials.gov/ct2/show/NCT02364999
Trastuzumab biosimilar
The phase 3 HERITAGE trial was a first-line, randomized, controlled trial that compared biosimilar trastuzumab-dkst (Ogivri) with trastuzumab in combination with taxane chemotherapy and then as maintenance monotherapy in 458 patients with HER2+ advanced breast cancer. The 24-week results, previously reported (JAMA. 2017 Jan 3;317[1]:37-47), showed a similar overall response rate with each agent when combined with chemotherapy. Rates of various AEs were essentially the same.
The 48-week results showed a median PFS of 11.1 months with trastuzumab-dkst and 11.1 months with trastuzumab (HR, 0.95; P = .842), reported senior investigator Hope S Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “The overall survival is immature but is impressive at over 80% at 52 weeks,” she noted.
Presence of overall response at 24 weeks correlated with duration of PFS at 48 weeks (biserial r = .752). “Additional patients achieved a response during the monotherapy portion of the treatment, which is intriguing and clearly emphasizes the importance of monotherapy, as well as the importance of having alternate agents at lower cost available,” Dr Rugo commented.
Common AEs through week 48 were much the same as those seen at week 24, with few additional [events] occurring during monotherapy. “No new safety issues were observed, and in fact, toxicity during monotherapy was quite minor,” she noted. “One thing that’s interesting here is that there was more arthralgia during the first 24 weeks with trastuzumab-dkst than with trastuzumab, but in monotherapy, this fell to a very low number and was identical between the 2 arms. Paclitaxel, which people stayed on for longer [with the biosimilar], may have been the cause of this.”
The 48-week rates of AEs of special interest – respiratory events, cardiac disorders, and infusion-related AEs – and of serious AEs were similar for the 2 agents.
“We didn’t see any additional serious cardiac events during monotherapy,” Dr Rugo noted. Mean and median left ventricular ejection fraction over 48 weeks were similar, as was the rate of LVEF, which dropped below 50% (4.0% with trastuzumab-dkst and 3.3% with trastuzumab). The incidences of antidrug antibody and neutralizing antibody were also comparably low in both groups.
“HERITAGE data, now at week 48, supports trastuzumab-dkst as a biosimilar to trastuzumab in all approved indications,” Dr Rugo said. “Final overall survival will be assessed after 36 months or after 240 deaths, whichever occurs first. Based on current data, this is predicted to conclude by the end of 2018, with final overall survival data available next year.”
Dr Rugo emphasized that trastuzumab-dkst provides “an additional high-quality treatment option for patients with HER2+ breast cancers in any setting. This study shows that biosimilars offer the potential for worldwide cost savings and improved access to life-saving therapies. It’s sobering to think that the patients enrolled in this study would not otherwise have had access to continued trastuzumab therapy, and so many of them are still alive with longer follow-up.”
Funding Mylan sponsored the HERITAGE trial. Disclosures Dr Rugo disclosed that she receives travel, accommodations, and/or expenses from Mylan. Source Manikhas A et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial. ASCO 2018, Abstract 110. https://meetinglibrary.asco.org/record/161572/abstract. Clinical trial registry number NCT02472964 https://clinicaltrials.gov/ct2/show/NCT02472964
Filgrastim biosimilar
Investigators led by Nadia Harbeck, MD, PhD, head of the Breast Center and chair for Conservative Oncology in the department of OB&GYN at the University of Munich (Germany), compared efficacy of filgrastim-sndz (Zarxio), a biosimilar of filgrastim (recombinant granulocyte colony-stimulating factor, or G-CSF), in a trial population with that of a real-world population of women receiving chemotherapy for breast cancer.
Data for the former came from PIONEER, a phase 3, randomized, controlled trial among patients with nonmetastatic breast cancer undergoing docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy in the neoadjuvant or adjuvant setting (Ann Oncol. 2015;26[9]:1948-53). Data for the latter came from MONITOR-GCSF, a postmarketing, open-label, observational cohort study among patients from 12 European countries receiving chemotherapy for various solid and hematologic malignancies (Support Care Cancer. 2016;24[2]:911-25).
Dr Harbeck and her colleagues compared 217 women who had nonmetastatic breast cancer from the trial with 466 women who had any-stage breast cancer (42% metastatic) from the real-world cohort.
Results showed that the 6.2% rate of chemotherapy-induced febrile neutropenia in any cycle seen in the real-world population was much the same as the 5.1% rate seen previously in the trial/biosimilar population. Findings were similar for temperature exceeding 38.5°C in any cycle: 3.4% and 5.6%, respectively. The real-world population had a lower rate of severe neutropenia than did the trial population (19.5% and 74.3%) and higher rates of infection (15.5% and 7.9%) and hospitalization caused by febrile neutropenia (3.9% and 1.8%). Findings were essentially the same in cycle-level analyses.
The real-world cohort had many fewer any-severity safety events of special interest than did the trial cohort, such as musculoskeletal/connective tissue disorders (20 and 261 events, respectively) and skin/subcutaneous tissue disorders (5 and 258 events). “Seeing these data, you have to keep in mind that the patients received totally different chemotherapy. TAC chemotherapy has a lot of chemotherapy-associated side effects,” Dr Harbeck noted. “The other thing is that MONITOR was a real-world database, and one could assume that there is some underreporting of events that are not directly correlated to the events that are of particular interest.”
Additional results available only from the trial showed that no patients developed binding or neutralizing antibodies against G-CSF.
“From a clinician’s point of view, it is very reassuring that we did not see any other safety signals in the real-world data than we saw in the randomized controlled trial and the efficacy was very, very similar,” Dr Harbeck commented. “Having seen the discrepancies in the data, I think it’s important to have randomized controlled trials to assess and monitor AEs for registration purposes and real-world evidence to reflect the daily clinical routine,” she concluded.
Funding Sandoz sponsored the PIONEER and MONITOR-GCSF trials. Disclosures Dr Harbeck disclosed that she has a consulting or advisory role with Sandoz. Source Harbeck N et al. Comparison of efficacy and safety of biosimilar filgrastim in a RCT (PIONEER) and real-world practice (MONITOR-GCSF). ASCO 2018, Abstract 111. https://meetinglibrary.asco.org/record/161688/abstract. Clinical trial registry number NCT01519700 https://clinicaltrials.gov/ct2/show/NCT01519700
Biosimilars for three widely used oncology drugs showed efficacy and safety in lung cancer and breast cancer similar to those of the reference products, according to findings reported at the 2018 annual meeting of the American Society of Clinical Oncology in Chicago.
Oncology biosimilars for bevacizumab (Avastin), trastuzumab (Herceptin), and filgrastim (Neupogen and others) have yielded positive results in various patient populations and clinical settings, investigators reported at the annual ASCO meeting. The findings advance the promise of new agents that have no clinically meaningful differences in efficacy and safety when compared with their reference drugs but have substantially lower cost.
“Biosimilars are here,” said Michael A Thompson, MD, PhD, of Aurora Health Care in Milwaukee, Wisconsin, “[although] issues remain, including clinical decision support and pathway adoption, naming differences across the world, competition and lower prices versus the illusion of a free market, and adoption to decrease costs and increase value to our patients.” Dr Thompson was commenting during an invited discussion at the meeting. He is the medical director of the Early Phase Cancer Research Program and the Oncology Precision Medicine Program at Aurora Health (also see Commentary at end of article).
Bevacizumab biosimilar
The REFLECTIONS trial (NCT02364999) was a multinational, first-line, randomized, controlled trial among 719 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Patients were randomized to paclitaxel and carboplatin chemotherapy plus either bevacizumab (sourced from the European Union) or the candidate bevacizumab biosimilar PF-06439535 on a double-blind basis, followed by monotherapy with the same assigned agent.
The overall response rate by week 19, confirmed by week 25 – the trial’s primary endpoint – was 45.3% with the biosimilar and 44.6% with bevacizumab, reported lead author Mark A Socinski, MD, executive medical director of the Florida Hospital Cancer Institute in Orlando. The confidence interval (CI) for the risk difference fell within the equivalence margins set by European Union regulators (-13% and +13% for the 95% CI). And the confidence interval for the risk ratio fell within the equivalence margins set by the US Food and Drug Administration (0.73 and 1.37 for the 90% CI) and Japanese regulators (0.729 and 1.371 for the 95% CI).
Median progression-free survival (PFS) was 9.0 months with the biosimilar and 7.7 months with bevacizumab (hazard ratio [HR], 0.974; P = .814), and corresponding 1-year rates were 30.8% and 29.3%, respectively, Dr Socinski reported. Median overall survival was 18.4 months and 17.8 months (HR, 1.001; P = .991), and corresponding 1-year rates were 66.4% and 68.8%.
Rates of grade 3 or higher hypertension, cardiac disorders, and bleeding did not differ significantly with the 2 agents. Patients also had similar rates of grade 3 or higher serious adverse events (AEs) and of fatal (grade 5) serious AEs with the biosimilar and bevacizumab (5.3% and 5.9%, respectively).
“Similarity between PF-06439535 and bevacizumab-EU was demonstrated for the primary efficacy endpoint of overall response rate. ... There were no clinically meaningful differences in safety profile shown in this trial, and similar pharmacokinetic and immunogenicity results were seen across treatment groups,” Dr Socinski summarized. “These results confirm the similarity demonstrated in earlier analytical, nonclinical, and clinical studies of PF-06439535 with bevacizumab-EU.”
Funding Pfizer sponsored the REFLECTIONS trial. Disclosures Dr Socinski disclosed that his institution receives research funding from Pfizer. Source Socinski MA et al. A comparative clinical study of PF-06439535, a candidate bevacizumab biosimilar, and reference bevacizumab, in patients with advanced non-squamous non-small cell lung cancer. ASCO 2018, Abstract 109. https://meetinglibrary.asco.org/record/161702/abstract. Clinical trial registry number NCT02364999 https://clinicaltrials.gov/ct2/show/NCT02364999
Trastuzumab biosimilar
The phase 3 HERITAGE trial was a first-line, randomized, controlled trial that compared biosimilar trastuzumab-dkst (Ogivri) with trastuzumab in combination with taxane chemotherapy and then as maintenance monotherapy in 458 patients with HER2+ advanced breast cancer. The 24-week results, previously reported (JAMA. 2017 Jan 3;317[1]:37-47), showed a similar overall response rate with each agent when combined with chemotherapy. Rates of various AEs were essentially the same.
The 48-week results showed a median PFS of 11.1 months with trastuzumab-dkst and 11.1 months with trastuzumab (HR, 0.95; P = .842), reported senior investigator Hope S Rugo, MD, a clinical professor of medicine and director of the Breast Oncology Clinical Trials Program at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “The overall survival is immature but is impressive at over 80% at 52 weeks,” she noted.
Presence of overall response at 24 weeks correlated with duration of PFS at 48 weeks (biserial r = .752). “Additional patients achieved a response during the monotherapy portion of the treatment, which is intriguing and clearly emphasizes the importance of monotherapy, as well as the importance of having alternate agents at lower cost available,” Dr Rugo commented.
Common AEs through week 48 were much the same as those seen at week 24, with few additional [events] occurring during monotherapy. “No new safety issues were observed, and in fact, toxicity during monotherapy was quite minor,” she noted. “One thing that’s interesting here is that there was more arthralgia during the first 24 weeks with trastuzumab-dkst than with trastuzumab, but in monotherapy, this fell to a very low number and was identical between the 2 arms. Paclitaxel, which people stayed on for longer [with the biosimilar], may have been the cause of this.”
The 48-week rates of AEs of special interest – respiratory events, cardiac disorders, and infusion-related AEs – and of serious AEs were similar for the 2 agents.
“We didn’t see any additional serious cardiac events during monotherapy,” Dr Rugo noted. Mean and median left ventricular ejection fraction over 48 weeks were similar, as was the rate of LVEF, which dropped below 50% (4.0% with trastuzumab-dkst and 3.3% with trastuzumab). The incidences of antidrug antibody and neutralizing antibody were also comparably low in both groups.
“HERITAGE data, now at week 48, supports trastuzumab-dkst as a biosimilar to trastuzumab in all approved indications,” Dr Rugo said. “Final overall survival will be assessed after 36 months or after 240 deaths, whichever occurs first. Based on current data, this is predicted to conclude by the end of 2018, with final overall survival data available next year.”
Dr Rugo emphasized that trastuzumab-dkst provides “an additional high-quality treatment option for patients with HER2+ breast cancers in any setting. This study shows that biosimilars offer the potential for worldwide cost savings and improved access to life-saving therapies. It’s sobering to think that the patients enrolled in this study would not otherwise have had access to continued trastuzumab therapy, and so many of them are still alive with longer follow-up.”
Funding Mylan sponsored the HERITAGE trial. Disclosures Dr Rugo disclosed that she receives travel, accommodations, and/or expenses from Mylan. Source Manikhas A et al. Biosimilar trastuzumab-dkst monotherapy versus trastuzumab monotherapy after combination therapy: Toxicity, efficacy, and immunogenicity from the phase 3 Heritage trial. ASCO 2018, Abstract 110. https://meetinglibrary.asco.org/record/161572/abstract. Clinical trial registry number NCT02472964 https://clinicaltrials.gov/ct2/show/NCT02472964
Filgrastim biosimilar
Investigators led by Nadia Harbeck, MD, PhD, head of the Breast Center and chair for Conservative Oncology in the department of OB&GYN at the University of Munich (Germany), compared efficacy of filgrastim-sndz (Zarxio), a biosimilar of filgrastim (recombinant granulocyte colony-stimulating factor, or G-CSF), in a trial population with that of a real-world population of women receiving chemotherapy for breast cancer.
Data for the former came from PIONEER, a phase 3, randomized, controlled trial among patients with nonmetastatic breast cancer undergoing docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy in the neoadjuvant or adjuvant setting (Ann Oncol. 2015;26[9]:1948-53). Data for the latter came from MONITOR-GCSF, a postmarketing, open-label, observational cohort study among patients from 12 European countries receiving chemotherapy for various solid and hematologic malignancies (Support Care Cancer. 2016;24[2]:911-25).
Dr Harbeck and her colleagues compared 217 women who had nonmetastatic breast cancer from the trial with 466 women who had any-stage breast cancer (42% metastatic) from the real-world cohort.
Results showed that the 6.2% rate of chemotherapy-induced febrile neutropenia in any cycle seen in the real-world population was much the same as the 5.1% rate seen previously in the trial/biosimilar population. Findings were similar for temperature exceeding 38.5°C in any cycle: 3.4% and 5.6%, respectively. The real-world population had a lower rate of severe neutropenia than did the trial population (19.5% and 74.3%) and higher rates of infection (15.5% and 7.9%) and hospitalization caused by febrile neutropenia (3.9% and 1.8%). Findings were essentially the same in cycle-level analyses.
The real-world cohort had many fewer any-severity safety events of special interest than did the trial cohort, such as musculoskeletal/connective tissue disorders (20 and 261 events, respectively) and skin/subcutaneous tissue disorders (5 and 258 events). “Seeing these data, you have to keep in mind that the patients received totally different chemotherapy. TAC chemotherapy has a lot of chemotherapy-associated side effects,” Dr Harbeck noted. “The other thing is that MONITOR was a real-world database, and one could assume that there is some underreporting of events that are not directly correlated to the events that are of particular interest.”
Additional results available only from the trial showed that no patients developed binding or neutralizing antibodies against G-CSF.
“From a clinician’s point of view, it is very reassuring that we did not see any other safety signals in the real-world data than we saw in the randomized controlled trial and the efficacy was very, very similar,” Dr Harbeck commented. “Having seen the discrepancies in the data, I think it’s important to have randomized controlled trials to assess and monitor AEs for registration purposes and real-world evidence to reflect the daily clinical routine,” she concluded.
Funding Sandoz sponsored the PIONEER and MONITOR-GCSF trials. Disclosures Dr Harbeck disclosed that she has a consulting or advisory role with Sandoz. Source Harbeck N et al. Comparison of efficacy and safety of biosimilar filgrastim in a RCT (PIONEER) and real-world practice (MONITOR-GCSF). ASCO 2018, Abstract 111. https://meetinglibrary.asco.org/record/161688/abstract. Clinical trial registry number NCT01519700 https://clinicaltrials.gov/ct2/show/NCT01519700
Key clinical points Biosimilars for bevacizumab, trastuzumab, and filgrastim showed similar efficacy and safety compared with their reference drugs.
Major findings Bevacizumab In patients with advanced nonsquamous NSCLC, the ORR was 45.3% with a candidate bevacizumab biosimilar and 44.6% with bevacizumab. Trastuzumab In patients with HER2+ advanced breast cancer, 48-week median PFS was 11.1 months for both trastuzumab-dkst and trastuzumab. Filgrastim The rate of chemotherapy-induced febrile neutropenia among breast cancer patients given a biosimilar for filgrastim was 5.1% in a trial population and 6.2% in a real-world population.
Study details Randomized, controlled trials of first-line therapy among 719 patients with advanced nonsquamous NSCLC (REFLECTIONS trial with bevacizumab) and among 458 patients with HER2+ advanced breast cancer (HERITAGE trial with trastuzumab). Comparison of outcomes in a randomized, controlled trial among 217 patients with nonmetastatic breast cancer (PIONEER trial with filgrastim) and a real-world cohort study of 466 patients with any-stage breast cancer (MONITOR-GCSF with filgrastim).
Disclosures and sources See article text.
No boost in OS with addition of capecitabine for early TNBC
SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.
At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.
The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.
SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.
At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.
The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.
SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.
At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.
The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.
REPORTING FROM SABCS 2018
Study reveals long-term survival in MM patients
A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.
The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.
Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.
Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.
The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.
Factors associated with survival
Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).
Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).
The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.
They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.
Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:
- Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
- Had an IgA isotype (OR=1.53; P=0.004)
- Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
- Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
- Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
- Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
- Had a platelet count below 150,000/μL (OR=2.26; P<0.001).
Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.
Comparison to general population
Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.
With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.
The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”
“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”
Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.
A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.
The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.
Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.
Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.
The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.
Factors associated with survival
Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).
Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).
The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.
They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.
Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:
- Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
- Had an IgA isotype (OR=1.53; P=0.004)
- Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
- Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
- Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
- Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
- Had a platelet count below 150,000/μL (OR=2.26; P<0.001).
Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.
Comparison to general population
Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.
With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.
The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”
“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”
Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.
A retrospective study suggests one in seven patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant may live at least as long as similar individuals in the general population.
The study included more than 7,000 MM patients, and 14.3% of those patients were able to meet or exceed their expected survival based on data from matched subjects in the general population.
Researchers believe that figure may be even higher today, as more than 90% of patients in this study were treated in the era before novel therapies became available.
Saad Z. Usmani, MD, of the Levine Cancer Institute/Atrium Health in Charlotte, North Carolina, and his colleagues described this study in Blood Cancer Journal.
The researchers studied 7,291 patients with newly diagnosed MM who were up to 75 years old and eligible for treatment with high-dose melphalan and autologous stem cell transplant. The patients were treated on clinical trials in 10 countries.
Factors associated with survival
Patients who had achieved a complete response (CR) 1 year after diagnosis had better median progression-free survival (PFS) than patients who did not achieve a CR—3.3 years and 2.6 years, respectively (P<0.0001).
Patients with a CR also had better median overall survival (OS)—8.5 years and 6.3 years, respectively (P<0.0001).
The identification of early CR as a predictor of PFS and OS “underscores the importance of depth of response as we explore novel regimens for newly diagnosed MM along with MRD [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote.
They did acknowledge, however, that the patients studied were a selected group eligible for transplant and treated on trials.
Dr. Usmani and his colleagues also performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death. The results indicated that patients were less likely to be alive at 10 years if they:
- Were older than 65 (odds ratio [OR]for death, 1.87, P=0.002)
- Had an IgA isotype (OR=1.53; P=0.004)
- Had an albumin level lower than 3.5 g/dL (OR=1.36; P=0.023)
- Had a beta-2 microglobulin level of at least 3.5 mg/dL (OR=1.86; P<0.001)
- Had a serum creatinine level of at least 2 mg/dL (OR=1.77; P=0.005)
- Had a hemoglobin level below 10 g/dL (OR=1.55; P=0.003)
- Had a platelet count below 150,000/μL (OR=2.26; P<0.001).
Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.
Comparison to general population
Overall, the MM patients had a relative survival of about 0.9 compared with the matched general population. Relative survival was the ratio of observed survival among MM patients to expected survival in a population with comparable characteristics, such as nationality, age, and sex.
With follow-up out to about 20 years, the cure fraction—or the proportion of patients achieving or exceeding expected survival compared with the matched general population—was 14.3%.
The researchers noted that recent therapeutic advances “have re-ignited the debate on possible functional curability of a subset of MM patients. [T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s.”
“This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [a partial response] yet had good long-term survival.”
Dr. Usmani reported relationships with AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, SkylineDx, Array Biopharma, and Pharmacyclics.
New data further support curability of myeloma
finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.
Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.
Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.
The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.
Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta2-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).
Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.
Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.
Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.
Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”
Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.
SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..
finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.
Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.
Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.
The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.
Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta2-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).
Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.
Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.
Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.
Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”
Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.
SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..
finds a retrospective cohort study of the International Myeloma Working Group. That figure may be even higher today because more than 90% of patients in the study – the largest yet to look at outcome predictors in this population – were treated in the era before novel therapies became available.
Investigators led by Saad Z. Usmani, MD, director/chief of plasma cell disorders and director of clinical research (hematologic malignancies) at the Levine Cancer Institute/Atrium Health in Charlotte, N.C., studied 7,291 patients with newly diagnosed multiple myeloma who were up to 75 years old and eligible for high-dose melphalan and autologous stem cell transplant. The patients were treated in clinical trials in 10 countries.
Compared with counterparts who did not achieve complete response 1 year after diagnosis, patients who did had better median progression-free survival (3.3 vs. 2.6 years; P less than .0001) and median overall survival (8.5 vs. 6.3 years; P less than .0001), according to study results report in Blood Cancer Journal.
The investigators next performed multivariate analyses to assess clinical variables at diagnosis associated with 10-year survival as compared with 2-year death.
Results here indicated that patients were less likely to be alive at 10 years if they were older than 65 years (odds ratio for death, 1.87; P = .002); had an immunoglobulin A isotype (OR, 1.53; P = .004); had a low albumin level, defined as less than 3.5 g/dL (OR, 1.36; P = .023); had an elevated beta2-microglobulin level, defined as at least 3.5 mg/dL (OR, 1.86; P less than .001); had a higher serum creatinine level, defined as at least 2 mg/dL (OR, 1.77; P = .005); had a lower hemoglobin level, defined as less than 10 g/dL (OR, 1.55; P = .003); or had a lower platelet count, defined as less than 150,000/μL (OR, 2.26; P less than .001).
Cytogenetic abnormalities did not independently predict long-term survival, but these abnormalities were obtained only by conventional band karyotyping and were not available for some patients.
Overall, the cohort had a relative survival of about 0.9 when compared with the matched general population. With follow-up out to about 20 years, the cure fraction (proportion achieving or exceeding expected survival when compared with the matched general population) was 14.3%.
Identification of early complete response as a predictor of long-term survival “underscores the importance of depth of response as we explore novel regimens for newly diagnosed [multiple myeloma] along with [minimal residual disease] endpoints,” Dr. Usmani and his colleagues wrote while acknowledging that the patients studied were a selected group eligible for transplant and treated on trials.
Recent therapeutic advances “have reignited the debate on possible functional curability of a subset MM patients,” they noted. “[T]here are perhaps more effective drugs and drug classes in the clinician’s armamentarium than [were] available for MM patients being treated in the 1990s or even early 2000s. This may mean that the depth of response after induction therapy may continue to improve over time, potentially further improving the PFS/OS of [the] biologic subset who previously achieved [partial response] yet had good long-term survival.”
Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.
SOURCE: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123..
FROM BLOOD CANCER JOURNAL
Key clinical point: Some patients with newly diagnosed multiple myeloma eligible for transplant are likely now being cured.
Major finding: The cure fraction (proportion of patients achieving or exceeding expected survival compared with the matched general population) was 14.3%.
Study details: An international retrospective cohort study of 7,291 patients with newly diagnosed multiple myeloma eligible for high-dose melphalan and autologous stem cell transplant who were treated in clinical trials.
Disclosures: Dr. Usmani disclosed that he is a consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Takeda, Sanofi, and SkylineDx; receives speaker’s fees for Amgen, Celgene, Janssen, and Takeda; and receives research funding from Amgen, Array Biopharma, BMS, Celgene, Janssen, Pharmacyclics, Sanofi, and Takeda.
Source: Usmani SZ et al. Blood Cancer J. 2018 Nov 23;8(12):123.
Valve-in-valve TAVR benefits maintained at 3 years
SAN DIEGO – Early benefits of valve-in-valve transcatheter aortic valve replacement (TAVR) for patients with failing surgical aortic bioprosthetic valves are sustained for at least 3 years, based on results presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
Previously published data for the 365 patients from the PARTNER Valve-in-Valve study showed dramatic improvements at 30 days and 1 year in hemodynamic measures, mitral and tricuspid regurgitation, and quality of life (J Am Coll Cardiol. 2017;69:2253-62).
At the 3-year mark, about one-third of patients had died, reported lead investigator John G. Webb, MD, a professor at the University of British Columbia, Vancouver. “I think we can say that this reflects multiple comorbidities in this high-risk patient population with an STS [Society of Thoracic Surgery] risk score of 1.9%. Patients were selected for being at extreme risk,” he commented. “This is not unexpected. ... This is very comparable to what we saw in the early PARTNER trials as well.”
For survivors, however, the early benefits were still present and largely unattenuated at 3 years. For example, about half of patients were New York Heart Association (NYHA) class I at 30 days, at 1 year, and at 3 years. And Kansas City Cardiomyopathy Questionnaire (KCCQ) score, reflecting heart failure–related quality of life, averaged 70-77 at all three time points.
The proportion of patients needing yet another valve replacement (surgical or transcatheter), possibly signaling structural valve deterioration or degeneration, was less than 2% at 3 years, and hemodynamic parameters remained good.
Practical matters
Valve-in-valve TAVR need not be restricted to academic high-volume centers, according to Dr. Webb. “I run a regional program, and my regional program had a hub-and-spoke model where this was restricted to one institution, and four other institutions just did routine transfemoral TAVR. We had to give up that because these are some of the easiest TAVR procedures that we do. You have a radio-opaque valve, you know the angle, you know the size, it seals well, you don’t get annular rupture, you don’t need pacemakers very often.”
In addition, recent TCT registry data suggest that outcomes with valve-in-valve TAVR are better than those with native-valve TAVR, Dr. Webb noted. “There’s a knowledge base that’s required that routine TAVR operators may not have. But it can be taught, it can be learned, and it’s not a difficult procedure when you know how to do it.”
“This study is very, very useful for all of us,” commented press conference panelist Jeffrey J. Popma, MD, an interventional cardiologist at the Beth Israel Deaconess Medical Center in Boston. “But should we be reconsidering anticoagulation therapy in some of the valve-in-valve procedures? We have learned from the leaflet thrombosis data that one of the risk factors for that is a valve-in-valve procedure. Clinically, we have seen a few cases where thrombus does form in the nidus of all the material that’s there.”
“There was no sign of leaflet thrombosis playing a role in reintervention,” Dr. Webb replied. “[Reintervention] was performed for various reasons, including leaks and valves that were too small. So it wasn’t clear that leaflet thrombosis was a factor in this study. That being said, we weren’t looking for it; we didn’t have sensitive means [to detect it], we weren’t doing transesophageal echoes, we weren’t doing CTs.
“Personally, I suspect that maybe we should be routinely anticoagulating all of our valve implants,” he added. “We certainly do it for our mitral valves routinely, and although I can’t recommend it, I have to admit that we do do this for aortic valves in my particular center. But I have no data from this study to support that either way.”
Study details
The 365 patients studied came from both an initial registry and a continued access registry, but were largely similar on baseline characteristics. All underwent valve-in-valve TAVR with SAPIEN XT transcatheter heart valves.
Mortality in the cohort was 12.1% at 1 year, 22.2% at 2 years, and 32.7% at 3 years, according to results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. In contrast, the rate of stroke was stable over time, at 5.1%, 5.1%, and 6.2%, respectively.
Repeat valve replacement (either surgical or transcatheter) had been performed in 0.6% of patients at 1 year, 0.6% at 2 years, and 1.9% at 3 years. “I think this is comparable to [what is seen in] surgical series,” Dr. Webb commented.
Between 30 days and 3 years, there were insignificant decreases in total aortic regurgitation that was moderate or worse in severity (from 2.9% to 2.5%) and paravalvular aortic regurgitation of these severities (from 2.6% to 1.4%). Although the valve used was older, “still, we had excellent sealing and aortic insufficiency was not a problem with these patients,” he noted.
In “interesting” findings, prevalence of mitral regurgitation that was moderate or worse continued falling, from 17.2% at 30 days to 8.6% at 3 years, and prevalence of tricuspid regurgitation that was moderate or worse did as well, from 21.8% to 18.8%.
“I was a little suspicious this was just a survival issue, that patients with severe mitral or tricuspid regurgitation died and, consequently, the average patient was less likely to have [these findings]. But the analysis that’s being done is linear mixed-effects analysis, which accounts for the survival bias,” Dr. Webb said.
The reasons for these trends are unknown, but possibly improved left ventricular function led to functional (rather than structural) improvements in mitral and tricuspid regurgitation.
At 3 years, proportions of patients with various NYHA classes were much the same as they had been at 30 days: class I (51.4% vs. 53.9%), class II (34.6% vs. 35.7%), and class III (13.0% vs. 9.2%). Similarly, the mean KCCQ overall summary score at 30 days (70.8) was sustained at 3 years (73.1).
Risk of death did not differ significantly according to the surgical valve size as labeled, the surgical valve true internal dimensions, the mode of valve failure, the approach used (transfemoral vs. transthoracic), or the residual gradient after valve implantation.
Analysis of the registry data is ongoing. For example, the investigators will be looking more closely at determinants of outcomes, such as additional characteristics of the surgical valve alone and in combination with those of the new valve. “We are all very aware that a lot of the outcomes have to do with what surgical valves you had to begin with. I think that is really critical – what surgical valve is in there,” he said.
Dr. Webb reported that he receives grant/research support and honoraria from, and is on the steering committee for, Edwards Lifesciences. The registry is sponsored by Edwards Lifesciences.
SAN DIEGO – Early benefits of valve-in-valve transcatheter aortic valve replacement (TAVR) for patients with failing surgical aortic bioprosthetic valves are sustained for at least 3 years, based on results presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
Previously published data for the 365 patients from the PARTNER Valve-in-Valve study showed dramatic improvements at 30 days and 1 year in hemodynamic measures, mitral and tricuspid regurgitation, and quality of life (J Am Coll Cardiol. 2017;69:2253-62).
At the 3-year mark, about one-third of patients had died, reported lead investigator John G. Webb, MD, a professor at the University of British Columbia, Vancouver. “I think we can say that this reflects multiple comorbidities in this high-risk patient population with an STS [Society of Thoracic Surgery] risk score of 1.9%. Patients were selected for being at extreme risk,” he commented. “This is not unexpected. ... This is very comparable to what we saw in the early PARTNER trials as well.”
For survivors, however, the early benefits were still present and largely unattenuated at 3 years. For example, about half of patients were New York Heart Association (NYHA) class I at 30 days, at 1 year, and at 3 years. And Kansas City Cardiomyopathy Questionnaire (KCCQ) score, reflecting heart failure–related quality of life, averaged 70-77 at all three time points.
The proportion of patients needing yet another valve replacement (surgical or transcatheter), possibly signaling structural valve deterioration or degeneration, was less than 2% at 3 years, and hemodynamic parameters remained good.
Practical matters
Valve-in-valve TAVR need not be restricted to academic high-volume centers, according to Dr. Webb. “I run a regional program, and my regional program had a hub-and-spoke model where this was restricted to one institution, and four other institutions just did routine transfemoral TAVR. We had to give up that because these are some of the easiest TAVR procedures that we do. You have a radio-opaque valve, you know the angle, you know the size, it seals well, you don’t get annular rupture, you don’t need pacemakers very often.”
In addition, recent TCT registry data suggest that outcomes with valve-in-valve TAVR are better than those with native-valve TAVR, Dr. Webb noted. “There’s a knowledge base that’s required that routine TAVR operators may not have. But it can be taught, it can be learned, and it’s not a difficult procedure when you know how to do it.”
“This study is very, very useful for all of us,” commented press conference panelist Jeffrey J. Popma, MD, an interventional cardiologist at the Beth Israel Deaconess Medical Center in Boston. “But should we be reconsidering anticoagulation therapy in some of the valve-in-valve procedures? We have learned from the leaflet thrombosis data that one of the risk factors for that is a valve-in-valve procedure. Clinically, we have seen a few cases where thrombus does form in the nidus of all the material that’s there.”
“There was no sign of leaflet thrombosis playing a role in reintervention,” Dr. Webb replied. “[Reintervention] was performed for various reasons, including leaks and valves that were too small. So it wasn’t clear that leaflet thrombosis was a factor in this study. That being said, we weren’t looking for it; we didn’t have sensitive means [to detect it], we weren’t doing transesophageal echoes, we weren’t doing CTs.
“Personally, I suspect that maybe we should be routinely anticoagulating all of our valve implants,” he added. “We certainly do it for our mitral valves routinely, and although I can’t recommend it, I have to admit that we do do this for aortic valves in my particular center. But I have no data from this study to support that either way.”
Study details
The 365 patients studied came from both an initial registry and a continued access registry, but were largely similar on baseline characteristics. All underwent valve-in-valve TAVR with SAPIEN XT transcatheter heart valves.
Mortality in the cohort was 12.1% at 1 year, 22.2% at 2 years, and 32.7% at 3 years, according to results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. In contrast, the rate of stroke was stable over time, at 5.1%, 5.1%, and 6.2%, respectively.
Repeat valve replacement (either surgical or transcatheter) had been performed in 0.6% of patients at 1 year, 0.6% at 2 years, and 1.9% at 3 years. “I think this is comparable to [what is seen in] surgical series,” Dr. Webb commented.
Between 30 days and 3 years, there were insignificant decreases in total aortic regurgitation that was moderate or worse in severity (from 2.9% to 2.5%) and paravalvular aortic regurgitation of these severities (from 2.6% to 1.4%). Although the valve used was older, “still, we had excellent sealing and aortic insufficiency was not a problem with these patients,” he noted.
In “interesting” findings, prevalence of mitral regurgitation that was moderate or worse continued falling, from 17.2% at 30 days to 8.6% at 3 years, and prevalence of tricuspid regurgitation that was moderate or worse did as well, from 21.8% to 18.8%.
“I was a little suspicious this was just a survival issue, that patients with severe mitral or tricuspid regurgitation died and, consequently, the average patient was less likely to have [these findings]. But the analysis that’s being done is linear mixed-effects analysis, which accounts for the survival bias,” Dr. Webb said.
The reasons for these trends are unknown, but possibly improved left ventricular function led to functional (rather than structural) improvements in mitral and tricuspid regurgitation.
At 3 years, proportions of patients with various NYHA classes were much the same as they had been at 30 days: class I (51.4% vs. 53.9%), class II (34.6% vs. 35.7%), and class III (13.0% vs. 9.2%). Similarly, the mean KCCQ overall summary score at 30 days (70.8) was sustained at 3 years (73.1).
Risk of death did not differ significantly according to the surgical valve size as labeled, the surgical valve true internal dimensions, the mode of valve failure, the approach used (transfemoral vs. transthoracic), or the residual gradient after valve implantation.
Analysis of the registry data is ongoing. For example, the investigators will be looking more closely at determinants of outcomes, such as additional characteristics of the surgical valve alone and in combination with those of the new valve. “We are all very aware that a lot of the outcomes have to do with what surgical valves you had to begin with. I think that is really critical – what surgical valve is in there,” he said.
Dr. Webb reported that he receives grant/research support and honoraria from, and is on the steering committee for, Edwards Lifesciences. The registry is sponsored by Edwards Lifesciences.
SAN DIEGO – Early benefits of valve-in-valve transcatheter aortic valve replacement (TAVR) for patients with failing surgical aortic bioprosthetic valves are sustained for at least 3 years, based on results presented at the Transcatheter Cardiovascular Therapeutics annual meeting.
Previously published data for the 365 patients from the PARTNER Valve-in-Valve study showed dramatic improvements at 30 days and 1 year in hemodynamic measures, mitral and tricuspid regurgitation, and quality of life (J Am Coll Cardiol. 2017;69:2253-62).
At the 3-year mark, about one-third of patients had died, reported lead investigator John G. Webb, MD, a professor at the University of British Columbia, Vancouver. “I think we can say that this reflects multiple comorbidities in this high-risk patient population with an STS [Society of Thoracic Surgery] risk score of 1.9%. Patients were selected for being at extreme risk,” he commented. “This is not unexpected. ... This is very comparable to what we saw in the early PARTNER trials as well.”
For survivors, however, the early benefits were still present and largely unattenuated at 3 years. For example, about half of patients were New York Heart Association (NYHA) class I at 30 days, at 1 year, and at 3 years. And Kansas City Cardiomyopathy Questionnaire (KCCQ) score, reflecting heart failure–related quality of life, averaged 70-77 at all three time points.
The proportion of patients needing yet another valve replacement (surgical or transcatheter), possibly signaling structural valve deterioration or degeneration, was less than 2% at 3 years, and hemodynamic parameters remained good.
Practical matters
Valve-in-valve TAVR need not be restricted to academic high-volume centers, according to Dr. Webb. “I run a regional program, and my regional program had a hub-and-spoke model where this was restricted to one institution, and four other institutions just did routine transfemoral TAVR. We had to give up that because these are some of the easiest TAVR procedures that we do. You have a radio-opaque valve, you know the angle, you know the size, it seals well, you don’t get annular rupture, you don’t need pacemakers very often.”
In addition, recent TCT registry data suggest that outcomes with valve-in-valve TAVR are better than those with native-valve TAVR, Dr. Webb noted. “There’s a knowledge base that’s required that routine TAVR operators may not have. But it can be taught, it can be learned, and it’s not a difficult procedure when you know how to do it.”
“This study is very, very useful for all of us,” commented press conference panelist Jeffrey J. Popma, MD, an interventional cardiologist at the Beth Israel Deaconess Medical Center in Boston. “But should we be reconsidering anticoagulation therapy in some of the valve-in-valve procedures? We have learned from the leaflet thrombosis data that one of the risk factors for that is a valve-in-valve procedure. Clinically, we have seen a few cases where thrombus does form in the nidus of all the material that’s there.”
“There was no sign of leaflet thrombosis playing a role in reintervention,” Dr. Webb replied. “[Reintervention] was performed for various reasons, including leaks and valves that were too small. So it wasn’t clear that leaflet thrombosis was a factor in this study. That being said, we weren’t looking for it; we didn’t have sensitive means [to detect it], we weren’t doing transesophageal echoes, we weren’t doing CTs.
“Personally, I suspect that maybe we should be routinely anticoagulating all of our valve implants,” he added. “We certainly do it for our mitral valves routinely, and although I can’t recommend it, I have to admit that we do do this for aortic valves in my particular center. But I have no data from this study to support that either way.”
Study details
The 365 patients studied came from both an initial registry and a continued access registry, but were largely similar on baseline characteristics. All underwent valve-in-valve TAVR with SAPIEN XT transcatheter heart valves.
Mortality in the cohort was 12.1% at 1 year, 22.2% at 2 years, and 32.7% at 3 years, according to results reported at the meeting, which is sponsored by the Cardiovascular Research Foundation. In contrast, the rate of stroke was stable over time, at 5.1%, 5.1%, and 6.2%, respectively.
Repeat valve replacement (either surgical or transcatheter) had been performed in 0.6% of patients at 1 year, 0.6% at 2 years, and 1.9% at 3 years. “I think this is comparable to [what is seen in] surgical series,” Dr. Webb commented.
Between 30 days and 3 years, there were insignificant decreases in total aortic regurgitation that was moderate or worse in severity (from 2.9% to 2.5%) and paravalvular aortic regurgitation of these severities (from 2.6% to 1.4%). Although the valve used was older, “still, we had excellent sealing and aortic insufficiency was not a problem with these patients,” he noted.
In “interesting” findings, prevalence of mitral regurgitation that was moderate or worse continued falling, from 17.2% at 30 days to 8.6% at 3 years, and prevalence of tricuspid regurgitation that was moderate or worse did as well, from 21.8% to 18.8%.
“I was a little suspicious this was just a survival issue, that patients with severe mitral or tricuspid regurgitation died and, consequently, the average patient was less likely to have [these findings]. But the analysis that’s being done is linear mixed-effects analysis, which accounts for the survival bias,” Dr. Webb said.
The reasons for these trends are unknown, but possibly improved left ventricular function led to functional (rather than structural) improvements in mitral and tricuspid regurgitation.
At 3 years, proportions of patients with various NYHA classes were much the same as they had been at 30 days: class I (51.4% vs. 53.9%), class II (34.6% vs. 35.7%), and class III (13.0% vs. 9.2%). Similarly, the mean KCCQ overall summary score at 30 days (70.8) was sustained at 3 years (73.1).
Risk of death did not differ significantly according to the surgical valve size as labeled, the surgical valve true internal dimensions, the mode of valve failure, the approach used (transfemoral vs. transthoracic), or the residual gradient after valve implantation.
Analysis of the registry data is ongoing. For example, the investigators will be looking more closely at determinants of outcomes, such as additional characteristics of the surgical valve alone and in combination with those of the new valve. “We are all very aware that a lot of the outcomes have to do with what surgical valves you had to begin with. I think that is really critical – what surgical valve is in there,” he said.
Dr. Webb reported that he receives grant/research support and honoraria from, and is on the steering committee for, Edwards Lifesciences. The registry is sponsored by Edwards Lifesciences.
REPORTING FROM TCT 2018
Key clinical point: Early improvements in functional status and quality of life measures with valve-in-valve transcatheter aortic valve replacement are maintained longer term.
Major finding: Improvements at 30 days post procedure were maintained at 3 years post procedure; patients had similar distributions of New York Heart Association classes (for example, class I in 53.9% and 51.4%, respectively) and similar heart failure–related quality of life scores (70.8 vs. 73.1, P = .29).
Study details: A multicenter, prospective cohort study of 365 patients who underwent valve-in-valve transcatheter aortic valve replacement because of a failing surgical aortic bioprosthetic valve.
Disclosures: Dr. Webb reported that he receives grant/research support and honoraria from, and is on the steering committee for Edwards Lifesciences. The registry is sponsored by Edwards Lifesciences.
Tumor burden in active surveillance for mRCC may inform treatment decisions
suggests an Italian cohort study.
Investigators led by Davide Bimbatti, MD, of Azienda Ospedaliera Universitaria Integrata in Verona, Italy, retrospectively studied 52 patients with mRCC who started active surveillance as their initial strategy for disease management. They assessed three predictors of outcomes: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, number of metastatic sites, and tumor burden.
Patients remained on active surveillance for a median of 18.3 months and had a median total overall survival of 80.1 months, according to study results published in Urologic Oncology. Fully 69.2% started first-line systemic therapy during a median follow-up of 38.5 months.
The only baseline factor predicting time on active surveillance was IMDC class (hazard ratio, 2.15; P = .011).
An increasing number of metastatic sites during active surveillance was associated with poorer total overall survival (HR, 2.86; P = .010) and a trend toward poorer postsurveillance overall survival (HR, 2.37; P = .060).
Increasing tumor burden, measured as the sum in millimeters of the longest tumor diameter of each measurable lesion, during active surveillance was associated with both poorer total overall survival (HR, 1.16; P = .024) and poorer postsurveillance overall survival (HR, 1.21; P = .004).
Finally, an IMDC class of good or intermediate versus poor at the start of systemic therapy was a favorable predictor (HR, 0.07; P = .010; and HR, 0.12; P = .044, respectively) and an increase in tumor burden was an unfavorable predictor (HR, 1.26; P = .005) of postsurveillance overall survival.
“Our study confirms that active surveillance is a safe option for certain patients, with a median time on surveillance of 1.5 years delaying the beginning of systemic therapies and avoiding drug-related toxicities, with a median overall survival greater than 6.5 years,” wrote Dr. Bimbatti and coinvestigators.
“During active surveillance, patients rarely show any deterioration of the IMDC prognostic class. Meanwhile, the tumor burden changes, more than the increase of metastatic sites, account for the heterogeneity of the disease and may help physicians to make decisions about the early termination of active surveillance and the start of systemic therapy,” they concluded.
SOURCE: Bimbatti D et al. Urol Oncol. 2018 Oct 6. doi: 10.1016/j.urolonc.2018.08.018.
suggests an Italian cohort study.
Investigators led by Davide Bimbatti, MD, of Azienda Ospedaliera Universitaria Integrata in Verona, Italy, retrospectively studied 52 patients with mRCC who started active surveillance as their initial strategy for disease management. They assessed three predictors of outcomes: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, number of metastatic sites, and tumor burden.
Patients remained on active surveillance for a median of 18.3 months and had a median total overall survival of 80.1 months, according to study results published in Urologic Oncology. Fully 69.2% started first-line systemic therapy during a median follow-up of 38.5 months.
The only baseline factor predicting time on active surveillance was IMDC class (hazard ratio, 2.15; P = .011).
An increasing number of metastatic sites during active surveillance was associated with poorer total overall survival (HR, 2.86; P = .010) and a trend toward poorer postsurveillance overall survival (HR, 2.37; P = .060).
Increasing tumor burden, measured as the sum in millimeters of the longest tumor diameter of each measurable lesion, during active surveillance was associated with both poorer total overall survival (HR, 1.16; P = .024) and poorer postsurveillance overall survival (HR, 1.21; P = .004).
Finally, an IMDC class of good or intermediate versus poor at the start of systemic therapy was a favorable predictor (HR, 0.07; P = .010; and HR, 0.12; P = .044, respectively) and an increase in tumor burden was an unfavorable predictor (HR, 1.26; P = .005) of postsurveillance overall survival.
“Our study confirms that active surveillance is a safe option for certain patients, with a median time on surveillance of 1.5 years delaying the beginning of systemic therapies and avoiding drug-related toxicities, with a median overall survival greater than 6.5 years,” wrote Dr. Bimbatti and coinvestigators.
“During active surveillance, patients rarely show any deterioration of the IMDC prognostic class. Meanwhile, the tumor burden changes, more than the increase of metastatic sites, account for the heterogeneity of the disease and may help physicians to make decisions about the early termination of active surveillance and the start of systemic therapy,” they concluded.
SOURCE: Bimbatti D et al. Urol Oncol. 2018 Oct 6. doi: 10.1016/j.urolonc.2018.08.018.
suggests an Italian cohort study.
Investigators led by Davide Bimbatti, MD, of Azienda Ospedaliera Universitaria Integrata in Verona, Italy, retrospectively studied 52 patients with mRCC who started active surveillance as their initial strategy for disease management. They assessed three predictors of outcomes: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, number of metastatic sites, and tumor burden.
Patients remained on active surveillance for a median of 18.3 months and had a median total overall survival of 80.1 months, according to study results published in Urologic Oncology. Fully 69.2% started first-line systemic therapy during a median follow-up of 38.5 months.
The only baseline factor predicting time on active surveillance was IMDC class (hazard ratio, 2.15; P = .011).
An increasing number of metastatic sites during active surveillance was associated with poorer total overall survival (HR, 2.86; P = .010) and a trend toward poorer postsurveillance overall survival (HR, 2.37; P = .060).
Increasing tumor burden, measured as the sum in millimeters of the longest tumor diameter of each measurable lesion, during active surveillance was associated with both poorer total overall survival (HR, 1.16; P = .024) and poorer postsurveillance overall survival (HR, 1.21; P = .004).
Finally, an IMDC class of good or intermediate versus poor at the start of systemic therapy was a favorable predictor (HR, 0.07; P = .010; and HR, 0.12; P = .044, respectively) and an increase in tumor burden was an unfavorable predictor (HR, 1.26; P = .005) of postsurveillance overall survival.
“Our study confirms that active surveillance is a safe option for certain patients, with a median time on surveillance of 1.5 years delaying the beginning of systemic therapies and avoiding drug-related toxicities, with a median overall survival greater than 6.5 years,” wrote Dr. Bimbatti and coinvestigators.
“During active surveillance, patients rarely show any deterioration of the IMDC prognostic class. Meanwhile, the tumor burden changes, more than the increase of metastatic sites, account for the heterogeneity of the disease and may help physicians to make decisions about the early termination of active surveillance and the start of systemic therapy,” they concluded.
SOURCE: Bimbatti D et al. Urol Oncol. 2018 Oct 6. doi: 10.1016/j.urolonc.2018.08.018.
FROM UROLOGIC ONCOLOGY
Key clinical point: Change in tumor burden during active surveillance for metastatic RCC is prognostic.
Major finding: Each millimeter increase in total tumor burden during surveillance was associated with a 16% higher risk of death overall and a 21% increase in risk of death after stopping surveillance and starting first-line systemic therapy.
Study details: Retrospective cohort study of 52 patients with metastatic RCC who started with active surveillance.
Disclosures: The authors declared having no conflicts of interest.
Source: Bimbatti D et al. Urol Oncol. 2018 Oct 6. doi: 10.1016/j.urolonc.2018.08.018.