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

Semin Oncol. 2018 Jan;45(1-2):52-57. doi: 10.1053/j.seminoncol.2018.04.005. Epub 2018 May 1.

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.

Keywords: immunotherapy; long-term survival; non–small cell lung cancer; survival mixture models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Cancer Vaccines / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cuba
  • Female
  • Humans
  • Immunotherapy / methods*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Models, Theoretical
  • Registries / statistics & numerical data
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • CIMAvax EGF
  • Cancer Vaccines
  • racotumomab