Evolution of end points for cancer immunotherapy trials

Ann Oncol. 2012 Sep:23 Suppl 8:viii47-52. doi: 10.1093/annonc/mds263.

Abstract

The effect of cancer immunotherapies is on the immune system and not directly on the tumour. The kinetics of immunotherapy are characterised by a cellular immune response followed by potential changes in tumour burden or patient survival. To adequately investigate immunotherapies in clinical trials, a new development paradigm including reconsideration of established end points addressing this biology is needed. Over the last 7 years, several initiatives across the cancer immunotherapy community were facilitated by the Cancer Research Institute Cancer Immunotherapy Consortium. They systematically evolved an immunotherapy-focused clinical development paradigm and proposed to redefine trial end points. On that basis, analysis of several large datasets generated throughout the immunotherapy community supports three novel end point proposals. First, results from T-cell immune response assays are highly variable and often nonreproducible. Harmonisation of assays can minimise this variability and support the investigation of the cellular immune response as a biomarker and testing it for clinical surrogacy. Secondly, immunotherapy induces novel patterns of the antitumour response not captured by World Health Organisation criteria or Response Evaluation Criteria in Solid Tumours. New immune-related response criteria were defined which more comprehensively capture all response patterns. Thirdly, survival curves in randomised immunotherapy trials can show a delayed separation, which can impact study results. Altered statistical models are needed to describe the hazard ratios as a function of time, and differentiate them before and after separation of curves to improve planning of phase III trials. Taken together, these recommendations may improve our tools for cancer immunotherapy investigations.

MeSH terms

  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use
  • Clinical Trials as Topic*
  • Endpoint Determination
  • Humans
  • Immunity, Cellular
  • Immunotherapy*
  • Models, Statistical
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Survival Analysis

Substances

  • Cancer Vaccines