Buti, Sebastiano

Abstract Background Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. Methods This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. Results Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node–only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. Conclusions Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.

5 Background: Management options for patients (pts) with advanced (locally advanced or metastatic) PeCa are limited. The GSRGT assembled an international cohort of pts with advanced PeCa treated with ICI to evaluate toxicity and clinical outcomes. Methods: We retrospectively collected data on pts with advanced PeCa receiving ≥1 cycle of ICI between 2015-2022 at 18 medical centers in the US, Europe, and Asia. Immune-related adverse events (irAE) were graded per the Common Terminology Criteria for Adverse Events v5.0. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Objective response rate (ORR) was determined by the clinical investigator per RECIST 1.1 criteria, whenever feasible. Results: Among 72 pts with advanced PeCa treated with ICI, 24 (33%) were Hispanic and 7 (10%) were Black. 60 (83%) pts had metastases while the remainder had locally advanced disease. The median age was 64 (inter-quartile range (IQR): 54,70) years and 48 (67%) had ECOG performance status ≥1. Most pts (n=60, 83%) were treated in the ≥2nd line setting and received pembrolizumab (n=23), nivolumab (n=15), cemiplimab (n=15), nivolumab and ipilimumab (n=7), or other anti-PD1/L1-based therapies (n=12). Among 37 pts with available data on HPV status, 24 (65%) were HPV+. 3 (4%) pts were HIV+. irAE of any grade occurred in 18 (25%) pts, 7 (10%) were grade ≥3, 7 (10%) required steroids, 6 (9%) required hospitalization, and 8 (11%) led to treatment discontinuation. The median OS and 24-month OS and median PFS and 24-month PFS were 9.4 (95%CI: 6.8, 12.8) months and 19.3% (95%CI: 9.2, 32.1) and 2.8 (95%CI: 2.1, 3.9) months and 11.2 % (95%CI: 4.9, 20.2), respectively. Among 66 pts evaluable for response, ORR was 7/66 (11%) (2 with complete response, 5 with partial response), and 16 (24%) pts had stable disease for a disease control rate of 35%. The median duration of response was 7.9 (IQR: 3, not reached) months. Conclusions: In the largest retrospective cohort of ICI-treated advanced PeCa, ICI showed no new safety signals, however, overall anti-tumor activity was limited. Future translational studies are needed to identify pts that are more likely to derive clinical benefit from ICI.