Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors

Author:

El Zarif Talal12ORCID,Nassar Amin H2,Pond Gregory R3,Zhuang Tony Zibo4,Master Viraj5,Nazha Bassel5ORCID,Niglio Scot6,Simon Nicholas7,Hahn Andrew W8ORCID,Pettaway Curtis A8,Tu Shi-Ming9,Abdel-Wahab Noha810,Velev Maud11,Flippot Ronan12,Buti Sebastiano13,Maruzzo Marco14,Mittra Arjun15,Gheeya Jinesh16,Yang Yuanquan16,Rodriguez Pablo Alvarez17,Castellano Daniel17,de Velasco Guillermo17,Roviello Giandomenico18,Antonuzzo Lorenzo1920ORCID,McKay Rana R21,Vincenzi Bruno22,Cortellini Alessio2223,Hui Gavin24,Drakaki Alexandra24,Glover Michael25,Khaki Ali Raza25ORCID,El-Am Edward26ORCID,Adra Nabil27,Mouhieddine Tarek H28,Patel Vaibhav28,Piedra Aida29,Gernone Angela30,Davis Nancy B31,Matthews Harrison32,Harrison Michael R32,Kanesvaran Ravindran33,Giudice Giulia Claire13,Barata Pedro34,Farolfi Alberto35,Lee Jae Lyun36,Milowsky Matthew I37,Stahlfeld Charlotte38,Appleman Leonard38ORCID,Kim Joseph W2,Freeman Dory1,Choueiri Toni K1ORCID,Spiess Philippe E39ORCID,Necchi Andrea40ORCID,Apolo Andrea B7,Sonpavde Guru P41ORCID

Affiliation:

1. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute , Boston, MA, USA ; Harvard Medical School, Boston, MA, USA

2. Yale Cancer Center, Yale School of Medicine , New Haven, CT, USA

3. Department of Oncology, McMaster University , Hamilton, ON, Canada

4. Department of Medicine, Emory University School of Medicine , Atlanta, GA, USA

5. Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute , Atlanta, GA, USA

6. New York University Grossman School of Medicine , New York, NY, USA

7. Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA

8. University of Texas MD Anderson Cancer Center , Houston, TX, USA

9. Division of Hematology and Oncology, University of Arkansas for Medical Sciences, Winthrop P. Rockefeller Cancer Institute , Little Rock, AR, USA

10. Assiut University Faculty of Medicine, Assiut University Hospitals , Assiut, Egypt

11. Département d’Innovation Thérapeutique et Essais Précoces, Gustave Roussy—Paris-Saclay University , Villejuif, France

12. Medical Oncology Department, Institute Gustave Roussy , Villejuif, France

13. Department of Medicine and Surgery, Oncology Unit, University Hospital of Parma , Parma, Italy

14. Oncology 1 Unit, Istituto Oncologico Veneto IOV—Istituto Di Ricovero e Cura a Carattere Scientifico , Padova, Italy

15. Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center , Columbus, OH, USA

16. Genitourinary Oncology Section, Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center—James Cancer Hospital , Columbus, OH, USA

17. Department of Medical Oncology, Hospital Universitario, 12 de Octubre , Madrid, Spain

18. Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence , Florence, Italy

19. Clinical Oncology Unit, Careggi University Hospital , Florence, Italy

20. Department of Experimental and Clinical Medicine, University of Florence , Florence, Italy

21. University of California San Diego , San Diego, CA, USA

22. Medical Oncology Department, Fondazione Policlinico Universitario Campus Bio-Medico , Rome, Italy

23. Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London , London, United Kingdom

24. University of California Los Angeles , Los Angeles, CA, USA

25. Division of Medical Oncology, Department of Medicine, Stanford University , Stanford, CA, USA

26. Department of Cardiovascular Medicine, Mayo Clinic , Rochester, MN, USA

27. Indiana University Simon Comprehensive Cancer Center , Indianapolis, IN, USA

28. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai , New York, NY, USA

29. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau , Barcelona, Spain

30. Unit of Medical Oncology Policlinico , Bari, Italy

31. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN, USA

32. Duke Cancer Institute Center for Prostate and Urologic Cancers , Durham, NC, USA

33. National Cancer Centre Singapore , Singapore

34. University Hospitals Seidman Cancer Center , Cleveland, OH, USA

35. Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori,” Meldola, Italy

36. University of Ulsan College of Medicine, Asan Medical Center , Seoul, Korea

37. University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC, USA

38. Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, PA, USA

39. Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute , Tampa, FL, USA

40. Department of Genitourinary Oncology, Vita-Salute San Raffaele University , Milan, Italy

41. Division of Medical Oncology, Advent Health Cancer Institute , Orlando, FL, USA

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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