Postprogression survival in patients with advanced non-small-cell lung cancer who receive second-line or third-line chemotherapy

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.