Is overall survival still the primary endpoint in maintenance non-small cell lung cancer studies? An analysis of phase III randomised trials Full Text
Translational Lung Cancer Research,  Review Article

Petrelli F. et al .– 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. In this study a literature review was conducted to examine whether post–progression survival (PPS) correlates with OS in maintenance trials. This is the first study that has explored the correlation of median OS with PFS and PPS in trials exploring maintenance therapy with both chemotherapy and molecular–targeted agents. The results indicate that, especially for trials including anti–EGFR TKIs, PPS is highly associated with OS (r=1). This correlation is strong even for chemotherapy arms (r=0.77). There is a weaker correlation between OS and PFS (r=0.37) and in particular, no correlation in chemotherapy trials (r=–0.06). Summarising all studies, however, PFS is a surrogate endpoint of survival for these trials exploring maintenance agents, and it represents a practical and reliable endpoint of activity.In relation to the strong effect of PPS on OS, PFS could be considered an appropriate endpoint for maintenance trials. However, a precise assessment of the disease course with a preplanned second–line therapy or an adjustment for treatments prescribed beyond progression is crucial.

Methods

  • In the present review, the median OS of modern (chemotherapy or molecular–targeted agents), phase III, and maintenance trials for patients with NSCLC not–progressing after 4–6 cycles of platinum–based therapy were divided into PFS and PPS.
  • The correlation of each of them with OS was then assessed through a regression analysis.
  • Evaluation of the PFS surrogacy of the OS was also performed.

Results

  • 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 (?PFS) and median OS (?OS) 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.

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