Estimating the percentage of patients with advanced melanoma achieving long-term survival with pembrolizumab (Pembro) treatment in KEYNOTE-006

Abstract

Background: The superior efficacy of pembro in prolonging overall survival (OS) over ipilimumab (ipi) has been demonstrated in the randomized phase 3 KEYNOTE-006 study (ClinicalTrials.gov, NCT01866319). Accumulating evidence suggests that immunotherapies such as pembro can even help some patients with advanced melanoma achieve long-term survival. The percentage of these long-term survivors over a defined population can be estimated by statistical methods, and herein is referred to as the “long-term survival” (LTS) rate of treatment. With the emergence of immunotherapies, LTS rate is increasingly important for quantifying the effectiveness and overall benefit of different treatment options. Methods: Since conventional parametric survival models do not account for the concept of LTS rate, an alternative, but well-established, class of statistical models called “cure-rate” survival models were used to estimate the percentage of long-term survivors. The intention-to-treat population of KEYNOTE-006 included 834 patients with advanced melanoma; 556 were randomized to pembro, and the remainder to ipi (control). LTS rates were estimated using the March 3, 2015, data cut and were subsequently updated using the December 3, 2015, data cut as validation. Results: With the initial data set, the pembro and ipi LTS rates were estimated as 54.9% (95% confidence interval [CI], 39.2%-63.7%) and 39.5% (23.5%-50.7%), respectively. With the subsequent data set, the pembro and ipi LTS rates were estimated as 49.2% (42.6%-55.3%) and 34.8% (26.5%-42.2%), respectively. The widths of CIs of the second data set narrowed substantially with longer follow-up. Conclusions: The estimated long-term benefits of pembro and ipi were reasonably consistent between the 2 data sets from KEYNOTE-006, suggesting that early estimates can be useful, with later estimates improving accuracy. The analysis suggests that about 50% of patients with advanced melanoma could achieve long-term survival with pembro treatment.