Abstract CT079: Durable responses to avelumab (anti-PD-L1) in patients with Merkel cell carcinoma progressed after chemotherapy: 1-year efficacy update
Authors: Kaufman Howard L. , Russell Jeffery S. , Hamid Omid , Bhatia Shailender , Terheyden Patrick , D’Angelo Sandra P. , Shih Kent C. , Lebbé Celeste , Milella Michele , Brownell Isaac , Lewis Karl D. , Lorch Jochen H. , Heydebreck Anja von , Mahnke Lisa , Nghiem Paul 
Published: July 2017

Abstract
Background: Merkel cell carcinoma (MCC), a rare, aggressive skin cancer, is a chemosensitive disease, but responses are seldom durable. Avelumab is a fully human anti-PD-L1 monoclonal antibody. In a phase 2 trial of avelumab in patients with previously treated metastatic MCC (mMCC), the objective response rate (ORR) after ≥6 months of follow-up was 31.8%, including complete response (CR) in 9.1%, the estimated proportion with duration of response (DOR) ≥6 months was 92%, and the 6-month progression-free survival (PFS) rate was 40% (95% CI 29-50) (Kaufman et al., Lancet Oncol 2016). Here we present updated efficacy data with ≥1 year of follow-up in all patients.
Methods: Patients with distant mMCC and prior progression on chemotherapy received avelumab 10 mg/kg IV Q2W until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 weeks (RECIST v1.1 by independent review). ORR, DOR, PFS, and overall survival (OS) were evaluated. Time-to-event endpoints were analyzed using Kaplan-Meier methodology. Safety data were not analyzed for this update.
Results: Patients with mMCC (N=88) were treated with avelumab. Median age was 72.5 years (range 33-88), and 53% had visceral disease. As of Sep 3, 2016, median follow-up was 16.4 months (range 12.0-25.3), and treatment was ongoing in 22% (n=19); main reasons for discontinuations were disease progression (n=44; 50%), death (n=7; 8%), adverse event (n=7; 8%), or withdrawal (n=4; 5%). ORR was 33.0% (95% CI 23.3-43.8) with 10 (11.4%) CRs and 19 (21.6%) partial responses, including 1 new CR and 1 patient improving from PR to CR since the 6-month analysis. The 6-month durable response rate was 30.6% (95% CI 20.9-40.3). Median DOR has not been reached (range 2.8-23.3+ months; 95% CI 18.0-not estimable), and responses were ongoing in 21/29 patients (72.4%) at the time of analysis. The estimated proportion of responders with ≥1-year duration of response was 74% (95% CI 53-87). Estimated 1-year PFS rate was 30% (95% CI 21-41) and 1-year OS rate was 52% (95% CI 41-62). Median OS was 12.9 months (95% CI 7.5-not estimable).
Conclusion: In longer-term follow-up from this study of avelumab in patients with distant metastatic MCC progressed after chemotherapy, the majority of responses were durable beyond 1 year and 2 new CRs were reported. Maturing PFS and OS data suggest long-term benefit in a proportion of patients. Clinical trial information: NCT02155647.
Citation Format: Howard L. Kaufman, Jeffery S. Russell, Omid Hamid, Shailender Bhatia, Patrick Terheyden, Sandra P. D’Angelo, Kent C. Shih, Celeste Lebbé, Michele Milella, Isaac Brownell, Karl D. Lewis, Jochen H. Lorch, Anja von Heydebreck, Lisa Mahnke, Paul Nghiem. Durable responses to avelumab (anti-PD-L1) in patients with Merkel cell carcinoma progressed after chemotherapy: 1-year efficacy update [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT079. doi:10.1158/1538-7445.AM2017-CT079