The effect of subsequent chemotherapy on overall survival (OS) has the potential to result in underestimation of the efficacy of an experimental treatment in clinical trials for advanced non-small-cell lung cancer (NSCLC). In this study, we investigated postprogression survival (PPS), defined as overall survival (OS) minus progression-free survival (PFS), in the second-line setting. PPS was highly associated with OS, and the induction rate for subsequent chemotherapy was associated with the duration of PPS. Our findings indicate that a beneficial effect of treatment on OS in patients with advanced NSCLC can be skewed by the effects of subsequent therapies in the second-line or third-line setting. Background: The increased availability of active agents has improved overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC). We previously showed that postprogression survival (PPS) is highly associated with OS in the first-line setting, but little is known about PPS in the salvage setting. In this study, we analyzed PPS in phase III trials in the second-line or third-line setting. Patients and Methods: A literature search identified 18 trials for previously treated patients with advanced NSCLC. We partitioned OS into progression-free survival (PFS) and PPS and evaluated the association between OS and either PFS or PPS. Correlation analysis to examine whether a treatment benefit for PFS carried over to OS was performed by calculation of incremental gains in OS and PFS at the trial level. Results: The average median PPS was longer than the average median PFS (5.4 and 2.6 months, respectively). The induction rate for subsequent chemotherapy after second-line or third-line treatment was related to the duration of PPS in linear regression analysis (r2 = 0.4813). Median OS was highly associated with median PPS but not with PFS (r = 0.94 and 0.51, respectively), and only a weak association between the treatment benefits for PFS and OS was detected (r = 0.29). Conclusions: Treatment benefit for OS in patients with advanced NSCLC can be skewed by the effects of subsequent therapies in the second-line or third-line setting. Whether PFS or OS is the more appropriate endpoint for trials in the salvage setting should be considered.
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