Survival Analysis in Patients with Metastatic Merkel Cell Carcinoma Treated with Avelumab

Adv Ther. 2019 Sep;36(9):2327-2341. doi: 10.1007/s12325-019-01034-0. Epub 2019 Jul 26.


Introduction: Complex underlying risk functions associated with immuno-oncology treatments have led to exploration of different methods (parametric survival, spline, landmark, and cure-fraction models) to estimate long-term survival outcomes. The objective of this study was to examine differences in estimated short- and long-term survival in previously treated metastatic Merkel cell carcinoma (mMCC) patients receiving avelumab, when using alternative extrapolation approaches.

Methods: Efficacy data from the phase 2 JAVELIN Merkel 200 trial (part A) with at least 12 months of follow-up were analyzed. Standard parametric survival analyses and analyses of overall survival (OS) as a function of surrogate outcomes comprised of response (landmark analyses) and progression-free survival plus post-progression survival (PFS + PPS) were used to project OS. Overall survival throughout lifetime was projected and compared with the observed OS data with at least 24 months of follow-up.

Results: Estimated OS from all three approaches provided a good fit to the observed OS curve from at least 12 months of follow-up. However, performance compared with OS data from at least 24 months showed that the landmark approach followed by PFS + PPS provided a better fit to the data as compared to standard parametric analysis. Mean life expectancy estimated with avelumab was 2.48 years with best-fitting parametric function (a log-normal distribution), 3.15 years with the landmark approach, and 3.54 years with PFS + PPS.

Conclusion: Although standard parametric survival analysis may provide a good fit to short-term survival, it appears to underestimate the long-term survival benefits associated with avelumab in mMCC. Extrapolations based on surrogate outcomes of response or progression predict OS outcomes from longer follow-up better and appear to provide more clinically plausible projections.

Funding: EMD Serono Inc, Rockland, MA, a business of Merck KGaA, Darmstadt, Germany.

Keywords: Avelumab; Extrapolation; Immuno-oncology; Landmark analyses; Merkel cell carcinoma; Overall survival; Post-progression survival; Standard parametric analysis.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Carcinoma, Merkel Cell / drug therapy*
  • Carcinoma, Merkel Cell / mortality
  • Disease-Free Survival
  • Female
  • Germany
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Progression-Free Survival*
  • Risk Assessment
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • avelumab

Associated data

  • figshare/10.6084/m9.figshare.8834429