Iterative parameter estimation (IPE) and rank-preserving structural failure time (RPSFT) analyses, both considered to be the best choice among correction analytics for evaluating the impact of crossover on overall survival, suggest that regorafenib has a greater overall survival benefit in patients with advanced gastrointestinal stromal tumor (GIST) than noted in the intention-to-treat (ITT) analysis. The findings of these exploratory analyses were presented at the 2016 Gastrointestinal Cancers Symposium in San Francisco, CA.1

The GRID trial demonstrated that regorafenib improved progression-free survival compared with placebo in patients with advanced GIST after failure of at least imatinib and sunitinib, but there was no benefit on significant benefit or overall survival.

When analyzing the impact of crossover on overall survival among the 85% of placebo patients crossing over to regorafenib, researchers observed a positive trend toward an overall survival benefit.

Therefore, researchers conducted various exploratory analyses to better estimate the effect of crossover from placebo to regorafenib using 3 different approaches.

Results showed that median overall survival at the time of final ITT analysis was 17.4 months with placebo and 17.4 months with regorafenib (HR, 0.91; 95% CI, 0.65 – 1.27).

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Using IPE correction, median overall survival was 11.1 months and 17.4 months, respectively (HR, 0.59; 95% CI, 0.42 – 0.82), and was 11.9 vs 17.4 months, respectively, with the RPSFT method (HR, 0.62; 95% CI, 0.44 – 0.87).

“Such sensitivity analytics are needed to understand fully the benefits of active drugs in crossover trials,” the authors concluded.

Reference

  1. Demetri GD, Reichardt P, Kang Y-K, et al. Final overall survival (OS) analysis with modeling of crossover impact in the phase III GRID trial of regorafenib vs placebo in advanced gastrointestinal stromal tumors (GIST). J Clin Oncol. 2016;34 (suppl 4S; abstr 156).