Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors
Authors: El Zarif Talal , Nassar Amin H , Pond Gregory R , Zhuang Tony Zibo , Master Viraj , Nazha Bassel , Niglio Scot , Simon Nicholas , Hahn Andrew W , Pettaway Curtis A , Tu Shi-Ming , Abdel-Wahab Noha , Velev Maud , Flippot Ronan , Buti Sebastiano , Maruzzo Marco , Mittra Arjun , Gheeya Jinesh , Yang Yuanquan , Rodriguez Pablo Alvarez , Castellano Daniel , de Velasco Guillermo , Roviello Giandomenico , Antonuzzo Lorenzo , McKay Rana R , Vincenzi Bruno , Cortellini Alessio , Hui Gavin , Drakaki Alexandra , Glover Michael , Khaki Ali Raza , El-Am Edward , Adra Nabil , Mouhieddine Tarek H , Patel Vaibhav , Piedra Aida , Gernone Angela , Davis Nancy B , Matthews Harrison , Harrison Michael R , Kanesvaran Ravindran , Giudice Giulia Claire , Barata Pedro , Farolfi Alberto , Lee Jae Lyun , Milowsky Matthew I , Stahlfeld Charlotte , Appleman Leonard , Kim Joseph W , Freeman Dory , Choueiri Toni K , Spiess Philippe E , Necchi Andrea , Apolo Andrea B , Sonpavde Guru P 
Published: August 2023

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.