Progression patterns and clinical outcomes after anti-PD-1 therapy failure in patients with cutaneous squamous cell carcinoma.

Abstract

e21521 Background: Cutaneous squamous cell carcinoma (CSCC) is the second most common cancer globally; however, advanced disease impacts a small subset of patients. Anti-PD-1 therapy yields durable responses, but progression develops in more than 30% of patients, with limited knowledge on outcomes after anti-PD-1 failure. This study investigates clinical outcomes in patients with CSCC following progression on anti-PD-1 therapy. Methods: A retrospective cohort study of patients with CSCC who progressed on anti-PD-1 therapy at the Dana-Farber Cancer Institute was performed. Patterns of progression, therapy type, and median time on therapy were summarized descriptively. Progression-free survival (PFS) was calculated from initiation of post anti-PD-1 therapy, and CSCC-specific death was estimated using Kaplan-Meier method. Results: Of 142 patients who received anti-PD-1 therapy, 54 developed disease progression, including 13 (24%) female, and 16 (30%) immunosuppressed. Primary head and neck location was the most common site in 30 patients (56%). AJCC 8 th edition CSCC stage at the time of starting anti-PD-1 was II/III in 27 (54%), and IV in 25 (46%). Median time on anti-PD-1 was 3 months (range, 1-27). Median follow-up time post-anti-PD-1 was 13 months (range, 1-58). Site of progression after anti-PD-1 failure was local in 14 (26%), locoregional nodal disease in 22 (41%), and metastatic in 18 (33%) of patients. There were 46 (85%) patients who received subsequent therapy after anti-PD-1, and 17 (32%) had anti-PD-1 re-challenged with 4 observed responses in evaluable patients. The median number of treatments post-anti-PD-1 was 1 (range, 0-11). The most common subsequent treatment following anti-PD-1 was a cetuximab containing regimen in 18 (39%) patients, with a response rate of (45%). The median PFS post-anti-PD-1 was 7 months (95% CI, 2.8-11.3), and median CSCC-specific survival was 27 months (95% CI, 12.3-45.9). Conclusions: In this cohort of patients with CSCC, the most common pattern of progression post-anti-PD-1 was non-metastatic progression involving regional lymph nodes. Cetuximab containing regimen was the most frequently utilized subsequent therapy. Larger studies are warranted to determine the best approach of treatment after anti-PD-1 therapy failure.