Responders to anti-PD1 therapy: Long-term outcomes and responses to retreatment in melanoma (mel).

Abstract

9513 Background: Little is known about patients (pts) who discontinue anti-PD1 therapy after a complete response (CR) outside of clinical trials. There are also limited data about retreatment with a second course of anti-PD1 upon disease progression. Methods: We retrospectively studied pts (n = 398) at MSKCC with unresectable mel (non-uveal) who received ≥1 dose of single-agent anti-PD1 and were followed ≥3 months (mos) after treatment cessation. CR was defined radiographically or by a negative biopsy of residual tissue. Overall survival (OS) and time to treatment failure (TTF, time until next therapy or death) were calculated from time of CR. When to stop therapy and whether to retreat after progressive disease (PD) were at the discretion of the treating oncologist. A subset of pts received a second course of single-agent anti-PD1 ≥3 months after initial discontinuation; retreated pts were evaluable if they had radiographic or clinical evaluation to assess retreatment efficacy. Results: 102 pts (25.6%) achieved CR (n = 89 radiographic, n = 13 pathologic). Median follow-up was 22.6 mos for survivors who had a CR. Estimated 3-year OS from time of CR was 82.5% (95% CI 67.4-91.0). For pts who had a CR, therapy was discontinued due to CR (n = 72), toxicity (n = 24), or other reasons (n = 6). The median duration of treatment for CR pts was 9.4 mos (range 1.6-36.1). 20 CR pts later had progressive disease (PD). Median TTF has not been reached; at 3-years the estimated treatment-free survival for CR pts was 72.3% (95% CI 60.2-81.3). 34 pts received a second course of anti-PD1 for PD after a median of 11.6 mos off treatment (range 3.5-28.6). Best responses to the second course of treatment were: 2 CRs (5.9%), 3 with tumor shrinkage (8.8%), 9 (26.5%) with SD, and 20 with PD (58.8%). Of these pts who had had a CR (n = 8) or some lesser degree of tumor shrinkage (n = 13) to the initial course of anti-PD1 treatment, only 1 and 2 pts responded, respectively, to retreatment. Median duration of retreatment was 10.9 wks. Conclusions: In this largest dataset to knowledge of mel pts treated with a second course of anti-PD1, response rate was low, even in pts who had achieved a response initially. Further study is needed into the necessary duration of initial anti-PD1 treatment and optimal strategies for initial responders who discontinue and later develop PD.