Projecting long term survival for avelumab in refractory Merkel cell carcinoma

Background: In the JAVELIN Merkel 200 trial, among 88 patients with previously treated metastatic Merkel cell carcinoma (mMCC), avelumab treatment resulted in an overall response rate of 33%, 86% and 45% of which lasted at least 6 months and one year respectively. While the durable response data underpins the survival benefit of avelumab in an indication with high unmet need, further follow-up is required to observe the long-term survival benefit. The objective of this study was to project potential long-term survival of avelumab by extrapolating survival data observed in the clinical trial. Methods: Observed overall survival (OS), time to progression (TTP) and post progression survival (PPS) data from the JAVELIN Merkel 200 trial (Part A), with =12 months of follow-up (09/03/2016), was analyzed. Statistical techniques that assume survival times for patients follow extrapolation of the trial data were applied. OS projections were explored using three different methods 1) extrapolating the observed OS of the overall population; 2) extrapolating the observed OS of responders and non-responders separately and then combining projections; 3) estimating OS as the sum of projected TTP and PPS. Predicted OS curves using 12-month data were verified against the 18-month data (03/24/2017). Average life expectancy and proportion of patients alive at 3, 5 and 10 years was estimated. Results: OS predicted from each of the three methods replicated the 18-month observed OS (40%, 95% CI: 29%,50%) reasonably well when appropriated distribution was selected. Long-term survival projections under these methods are presented in the table. Conclusions: The projected survival benefits for avelumab in mMCC are substantial, regardless of approach used. Statistical models can provide early insights to potential long-term survival benefits associated with avelumab while the trial data are still maturing.