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Differential effects of two therapeutic cancer vaccines on short- and long-term survival populations among patients with advanced lung cancer

Abstract:

Background: Progress in immunotherapy has revolutionized the treatment landscape for advanced lung cancer, with emerging evidence of patients experiencing long-term survivals. The goal of this study was to explore the existence of short- and long-term survival populations and to assess the effect of immunotherapy on them. Methods: Data from two randomized, multicenter, controlled clinical trials was used to evaluate the effect of two therapeutic vaccines (anti-idiotypic vaccine VAXIRA and anti-EGF vaccine CIMAVAX) on survival curves in advanced non–small cell lung cancer patients. Data were fitted to Kaplan-Meier, standard Weibull survival, and two-component Weibull mixture models. Bayesian Information Criterion was used for model selection. Results: VAXIRA did not modify, neither the fraction of patients with long-term survivals (0.18 in the control group v 0.19 with VAXIRA, P =.88), nor the median overall survival of the patients in the short-term survival subpopulation (6.8 v 7.8 months, P =.24). However, this vaccine showed great benefit for the patients belonging to the subpopulation of patients with long-term survival (33.8 v 76.6 months, P <.0001). CIMAVAX showed impact in the overall survival of both short- and long-term populations (6.8 v 8.8 months, P =.005 and 33.8 v 61.8 months, P =.007). It also increased the proportion of patients with long-term survival (from 0.18 to 0.28, P =.02). Conclusions: This study shows that therapeutic vaccines produce differential effects on short- and long-term survival populations and illustrates the application of advanced statistical methods to deal with the long-term evolution of patients with advanced lung cancer in the era of immunotherapy.