FDA Analysis Explores Relationship Between Response Rate and Survival at Trial and Patient Levels in Advanced NSCLC Studies
In a U.S. Food and Drug Administration (FDA) analysis of randomized trials in advanced non–small cell lung cancer (NSCLC) reported in the Journal of Clinical Oncology, Blumenthal et al found a strong correlation between response rate and progression-free survival at the trial level and a significant association between response and both progression-free and overall survival at the individual patient level.
Study Details
The study involved 14 trials of treatments for advanced NSCLC (N = 12,567) submitted to the FDA since 2003, including only randomized active-controlled trials with more than 150 patients.
Experimental regimens in the trials were crizotinib (Xalkori), afatinib (Gilotrif), erlotinib (Tarceva), nab-paclitaxel (Abraxane) plus carboplatin, vandetanib (Caprelsa), cetuximab (Erbitux), gefitinib (Iressa), bevacizumab (Avastin), pemetrexed (Alimta) plus cisplatin, and pemetrexed alone. Three trials evaluated targeted therapies in molecularly enriched populations (EGFR mutation in two, ALK rearrangement in one).
Correlation at Trial Level
In a trial-level analysis, there was a strong correlation between overall response rate and progression-free survival (R2 = 0.89, 95% confidence interval [CI] = 0.80–0.98), with no correlation being observed between response rate and overall survival (R2 = 0.09, 95% CI = 0-0.33) or between progression-free survival and overall survival (R2 = 0.08, 95% CI = 0–0.31).
Patient-Level Analysis
In the patient-level analysis, patients who achieved response had significantly better progression-free survival (hazard ratio [HR] = 0.40, 95% CI = 0.38–0.42) and overall survival (HR = 0.40, 95% CI = 0.38–0.43) vs nonresponders.
The investigators concluded: “On a trial level, there is a strong association between [overall response rate] and [progression-free survival]. An association between [overall response rate] and [overall survival] and between [progression-free survival] and [overall survival] was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better [progression-free survival] and [overall survival] compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on [overall response rate] may have a large [progression-free survival] effect.”
Gideon M. Blumenthal, MD, of the U.S. Food and Drug Administration, is the corresponding author for the Journal of Clinical Oncology article.
The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
