Analysis of response and survival in patients (pts) with ipilimumab (ipi)-refractory melanoma treated with pembrolizumab (pembro) in KEYNOTE-002

Abstract

Background: Treatment with checkpoint inhibitors can result in durable responses and deepening of responses over time with conversion of SD to PR or CR, and PR to CR. In the randomized KEYNOTE-002 study (NCT01704287), pembro 2 mg/kg or 10 mg/kg improved PFS (HR 0.57 and 0.50; P<0.0001 for both) vs chemo in pts with ipirefractory melanoma. In this post hoc analysis, we assessed evolution of response and survival for 361 pembro-treated pts. Methods: Pts were treated until disease progression (PD), unacceptable toxicity or investigator/ pt decision. Response (RECIST v1.1; investigator review) was assessed at wk 12, every 6 wk until wk 48, then every 12 wk, and confirmed by subsequent scan. Survival was assessed every 12 wk during follow-up. Pembro arms were combined given no difference in efficacy of doses. Results: As of 3 Feb 2017, median follow-up duration was 42.7mo. In pembro-treated pts, median PFS was 4.2 mo (95% CI 3.3-5.6), and 36-mo PFS rate was 16%. Median OS was 14.0 mo (11.8-16.2), and 36-mo OS rate was 30%. 99 of 361 pts had CR (n=29) or PR (n=70) for ORR of 27.4% (95% CI 22.9-32.3); 88 pts had SD. Median time to response was 2.9 mo. Of 29 pts with CR, 5 converted from SD, 21 from PR. Of 70 pts with PR, 28 converted from SD. Median time from SD to PR was 2.7 mo (range 0.9-25.2), from SD to CR was 6.9 mo (3.9-21.9), and from PR to CR was 8.0 mo (1.4- 25.2). Median DOR was not reached in pts with CR or PR (Table). Median duration of SD was 6.9mo (range 0.8+ to 38.8+). 9 (31%) pts with CR, 28 (40%) with PR and 63 (72%) with SD had subsequent PD; in these pts, median duration of CR was 17.1mo (5.5-36.1), PR 7.7 mo (2.0-31.8), and SD 5.8mo (2.7-25.3). Median PFS and OS were longer in pts with CR or PR (Table). Conclusions: Responses to pembro are durable and associated with prolonged OS in ipi-refractory melanoma. Even in these heavily pretreated pts best response can evolve over time, with late conversions from SD to PR/CR and PR to CR observed. (Table Presented).