Is overall survival still the primary endpoint in maintenance non-small cell lung cancer studies? An analysis of phase III randomised trials.

Abstract

In advanced non-small cell lung cancer (NSCLC), the increasing number of active compounds available in second line settings makes overall survival (OS) with maintenance treatment a not frequently observed endpoint. A literature review was conducted to examine whether post-progression survival (PPS) correlates with OS in maintenance trials. PPS was defined as median OS - median PFS. The authors used the coefficient of correlation (r) to assess the correlation between them. They also evaluated the surrogacy of PFS and OS. Ten trials with 11 arms were identified. Overall, a stronger correlation was observed between OS and PPS [Spearman rank correlation coefficient (r) =0.75] than OS and PFS time (r=0.37). The correlation of differences in median PFS (ΔPFS) and median OS (ΔOS) is 0.64 (P=0.0326). The slope of the regression line is 0.76, indicating that a maintenance therapy producing a one-month gain in PFS will yield an estimated three weeks prolongation in OS. PPS is strongly associated with OS because of intensive post-study further lines of treatment. However, improvements in PFS are moderately associated with improvements in OS. Hence, in this setting, PFS is a possible surrogate for OS.