Purpose:Antibodies blocking programmed death-1 receptor (anti-PD-1) produce durable responses in patients with metastatic melanoma, although >50% of patients ultimately experience disease progression. We aimed to identify prognostic factors and outcomes… Click to show full abstract
Purpose:Antibodies blocking programmed death-1 receptor (anti-PD-1) produce durable responses in patients with metastatic melanoma, although >50% of patients ultimately experience disease progression. We aimed to identify prognostic factors and outcomes to subsequent therapies in patients with metastatic melanoma that progressed on anti-PD-1. Materials and methods:We evaluated 383 patients who received anti-PD-1 (alone or in combination with ipilimumab [ipi]) for advanced melanoma between 2009 and 2019. Patient and disease characteristics at baseline and progression, factors correlating with survival after progression (SaP), subsequent therapies, objective response rate (ORR), overall survival (OS), and progression free survival (PFS) were assessed. Results:Of 383 patients, 247 experienced progression. At progression, most patients were stage IV M1c (49.0%), symptomatic from their disease (66.8%), and had progression at both new and existing lesions (39.3%). The median SaP was 206 days. There was no difference in SaP based on primary tumor subtype (cutaneous vs. non-cutaneous), receipt of prior therapy, prior ipi, or therapy type (anti-PD-1 vs. combination). However, significantly improved SaP correlated with clinical features at progression, including normal LDH (p 2-5cm, >5-8cm, and >8cm respectively; p Conclusions:We identified multiple clinical factors that correlated with SaP in patients with melanoma progressing on anti-PD-1. Further, we identified improved outcomes for subsequent BRAFi/MEKi or ipi + nivolumab vs. ipi alone. Finally, we identified a subgroup of patients with long-term SaP, potentially explaining the gap between PFS and OS demonstrated in many anti-PD-1 trials. Citation Format: James R. Patrinely, Laura X. Wang, Elizabeth J. Davis, Douglas B. Johnson. Outcomes after progression of disease with anti-PD-1/PDL1 therapy for advanced melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3154.
               
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