Abstract 3154: Outcomes after progression of disease with anti-PD-1/PDL1 therapy for advanced melanoma
Authors: Patrinely James R. , Wang Laura X. , Davis Elizabeth J. , Johnson Douglas B. 
Published: September 2020

Purpose:Antibodies blocking programmed death-1 receptor (anti-PD-1) produce durable responses in patients with metastatic melanoma, although &gt;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&lt;0.001), more favorable metastatic stage (median 639, 291, 233, and 76 days for stage IV M1a, M1b, M1c, and M1d, respectively; p&lt;0.001), initial response to anti-PD-1 (median 649, 439, and 117 days for complete/partial response, stable disease, and progressive disease, respectively; p&lt;0.001), mutation status (median 341, 316, 104, and 167 days for BRAF mutation [mut] with no prior BRAFi/MEKi, NRAS mut, BRAF mut with prior BRAFi/MEKi, BRAF/NRAS wild type, respectively; p=0.015), decreasing tumor bulk (median 557, 316, 261, and 98 days for largest tumor diameter 0-2cm, &gt;2-5cm, &gt;5-8cm, and &gt;8cm respectively; p&lt;0.001), and lack of symptoms (p&lt;0.001). After progression, patients received BRAFi/MEKi (n=41, ORR 58.6%), ipi (n=30, ORR 0%), BRAFi alone (n=13, ORR = 15.4%), ipi + nivolumab (n=11, ORR 27.3%), and MEKi alone (n=9, ORR 0%). The ORR to BRAFi/MEKi was higher in patients naïve to prior BRAFi or BRAFi/MEKi therapy compared to those with previous treatment (19/27, 70.4% vs. 5/14, 35.7%; p=0.03). Twenty seven patients (10.9%) had prolonged SaP, most commonly due to resection of a solitary progressing lesion (n=10) or benefit from subsequent BRAFi/MEKi (n=9).

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.