Late divergence of survival curves in cancer immunotherapy trials: interpretation and implications

Cancer Immunol Immunother. 2013 Oct;62(10):1547-51. doi: 10.1007/s00262-013-1458-y. Epub 2013 Aug 24.


Late divergence of survival curves of treated patients and controls is commonly seen in successful cancer immunotherapy trials. Although late survival curve divergence may be caused by a delayed action of therapy, it may also be related to early effects of the treatment. We suggest that late survival divergence most often reflects a specific benefit of therapy for patients who suffer from a comparatively slow progression of disease. The occurrence of delayed survival curve divergence has important implications for the statistical analysis of immunotherapy trials. Thus, it leads to non-proportional hazard ratios that make commonly used statistical tests, e.g., the logrank test, suboptimal. It is therefore suggested that the statistical analysis of immunotherapy trials primarily should be based on a test that compares the survival curves at or after a prespecified, fixed, late time point.

MeSH terms

  • Case-Control Studies
  • Humans
  • Immunotherapy*
  • Kaplan-Meier Estimate*
  • Models, Statistical
  • Neoplasms / immunology
  • Neoplasms / mortality*
  • Neoplasms / therapy*
  • Treatment Outcome