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TOPLINE:
METHODOLOGY:
- FDA approvals in the adjuvant setting for cancer immunotherapy are increasingly based on trials that use RFS as a surrogate endpoint for overall survival, largely because such a design allows for smaller, speedier trials.
- To test the validity of using RFS as a surrogate for overall survival in this setting, investigators conducted a meta-analysis of 15 phase 2 and 3 randomized controlled trials (RCTs) of adjuvant CTLA4 and anti–PD-1/PD-L1 blockers for melanoma, non–small cell lung cancer, renal cell cancer, and other tumors.
- The team used weighted regression at the arm and trial levels to assess the efficacy of RFS as a surrogate for overall survival.
- The strength of the association was quantified by weighted coefficients of determination (R2)12Dante MT Stdplz make sure all mentions of R’2’ are superscript, with a strong correlation considered to be R2 of 0.7 or higher.
- If there were strong correlations at both the arm and trial levels, RFS would be considered a robust surrogate endpoint for overall survival; however, if one of the correlations at the arm or trial level was not strong, RFS would not be considered a surrogate endpoint for overall survival.
TAKEAWAY:
- At the arm level, moderate and strong associations were observed between 2-year RFS and 3-year overall survival (R2, 0.58) and between 3-year RFS and 5-year overall survival (R2, 0.72; 95% confidence interval, 0.38-.00).
- At the trial level, a moderate association was observed between effect of treatment on RFS and overall survival (R2, 0.63).
- The findings were confirmed in several sensitivity analyses that were based on different trial phases, experimental arms, cancer types, and treatment strategies.
IN PRACTICE:
“Our meta-analysis failed to find a significantly strong association between RFS and OS in RCTs of adjuvant immunotherapy,” the authors concluded. “RFS should not be used as a surrogate endpoint for OS in this clinical context.” Instead, the finding indicates that overall survival is “the ideal primary endpoint” in this setting.
SOURCE:
The study, led by Yuanfang Li, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, was published in the Journal of the National Cancer Institute.
LIMITATIONS:
- Correlations were calculated from a relatively limited number of RCTs that involved different types of cancer, and overall survival data were not fully mature in some of the trials.
- The analysis did not include patient-level data.
DISCLOSURES:
- The work was funded by the National Natural Science Foundation of China and others.
- The investigators had no disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- FDA approvals in the adjuvant setting for cancer immunotherapy are increasingly based on trials that use RFS as a surrogate endpoint for overall survival, largely because such a design allows for smaller, speedier trials.
- To test the validity of using RFS as a surrogate for overall survival in this setting, investigators conducted a meta-analysis of 15 phase 2 and 3 randomized controlled trials (RCTs) of adjuvant CTLA4 and anti–PD-1/PD-L1 blockers for melanoma, non–small cell lung cancer, renal cell cancer, and other tumors.
- The team used weighted regression at the arm and trial levels to assess the efficacy of RFS as a surrogate for overall survival.
- The strength of the association was quantified by weighted coefficients of determination (R2)12Dante MT Stdplz make sure all mentions of R’2’ are superscript, with a strong correlation considered to be R2 of 0.7 or higher.
- If there were strong correlations at both the arm and trial levels, RFS would be considered a robust surrogate endpoint for overall survival; however, if one of the correlations at the arm or trial level was not strong, RFS would not be considered a surrogate endpoint for overall survival.
TAKEAWAY:
- At the arm level, moderate and strong associations were observed between 2-year RFS and 3-year overall survival (R2, 0.58) and between 3-year RFS and 5-year overall survival (R2, 0.72; 95% confidence interval, 0.38-.00).
- At the trial level, a moderate association was observed between effect of treatment on RFS and overall survival (R2, 0.63).
- The findings were confirmed in several sensitivity analyses that were based on different trial phases, experimental arms, cancer types, and treatment strategies.
IN PRACTICE:
“Our meta-analysis failed to find a significantly strong association between RFS and OS in RCTs of adjuvant immunotherapy,” the authors concluded. “RFS should not be used as a surrogate endpoint for OS in this clinical context.” Instead, the finding indicates that overall survival is “the ideal primary endpoint” in this setting.
SOURCE:
The study, led by Yuanfang Li, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, was published in the Journal of the National Cancer Institute.
LIMITATIONS:
- Correlations were calculated from a relatively limited number of RCTs that involved different types of cancer, and overall survival data were not fully mature in some of the trials.
- The analysis did not include patient-level data.
DISCLOSURES:
- The work was funded by the National Natural Science Foundation of China and others.
- The investigators had no disclosures.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- FDA approvals in the adjuvant setting for cancer immunotherapy are increasingly based on trials that use RFS as a surrogate endpoint for overall survival, largely because such a design allows for smaller, speedier trials.
- To test the validity of using RFS as a surrogate for overall survival in this setting, investigators conducted a meta-analysis of 15 phase 2 and 3 randomized controlled trials (RCTs) of adjuvant CTLA4 and anti–PD-1/PD-L1 blockers for melanoma, non–small cell lung cancer, renal cell cancer, and other tumors.
- The team used weighted regression at the arm and trial levels to assess the efficacy of RFS as a surrogate for overall survival.
- The strength of the association was quantified by weighted coefficients of determination (R2)12Dante MT Stdplz make sure all mentions of R’2’ are superscript, with a strong correlation considered to be R2 of 0.7 or higher.
- If there were strong correlations at both the arm and trial levels, RFS would be considered a robust surrogate endpoint for overall survival; however, if one of the correlations at the arm or trial level was not strong, RFS would not be considered a surrogate endpoint for overall survival.
TAKEAWAY:
- At the arm level, moderate and strong associations were observed between 2-year RFS and 3-year overall survival (R2, 0.58) and between 3-year RFS and 5-year overall survival (R2, 0.72; 95% confidence interval, 0.38-.00).
- At the trial level, a moderate association was observed between effect of treatment on RFS and overall survival (R2, 0.63).
- The findings were confirmed in several sensitivity analyses that were based on different trial phases, experimental arms, cancer types, and treatment strategies.
IN PRACTICE:
“Our meta-analysis failed to find a significantly strong association between RFS and OS in RCTs of adjuvant immunotherapy,” the authors concluded. “RFS should not be used as a surrogate endpoint for OS in this clinical context.” Instead, the finding indicates that overall survival is “the ideal primary endpoint” in this setting.
SOURCE:
The study, led by Yuanfang Li, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, was published in the Journal of the National Cancer Institute.
LIMITATIONS:
- Correlations were calculated from a relatively limited number of RCTs that involved different types of cancer, and overall survival data were not fully mature in some of the trials.
- The analysis did not include patient-level data.
DISCLOSURES:
- The work was funded by the National Natural Science Foundation of China and others.
- The investigators had no disclosures.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE NATIONAL CANCER INSTITUTE