(UroToday.com) The 2025 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between February 13th and 15th 2025, was host to the Poster Session C: Renal Cell Cancer; Adrenal, Penile, Testicular and Urethral Cancers. Dr. Amarnath Challapalli presented the Abstract 9: EPIC-B: Phase II trial of cemiplimab as first-line treatment in advanced penile carcinoma.
Patients with locally advanced or metastatic penile squamous cell carcinoma (la/mPC) have a poor prognosis with limited treatment options. The current standard of care remains platinum-based combination chemotherapy, which offers modest outcomes and significant toxicity. However, many patients are ineligible or unfit for chemotherapy, leaving them with few management options.
Programmed death-ligand 1 (PD-L1) is upregulated in 40–60% of penile cancers, supporting the rationale for immune checkpoint inhibitors in this setting. Cemiplimab, a programmed death-1 (PD-1) inhibitor approved for locally advanced or metastatic cutaneous squamous cell carcinoma (SCC), has shown promise in la/mPC. (1) Dr. Challapalli presented results from the EPIC-B trial, evaluating the efficacy and safety of cemiplimab as first-line treatment in this population.
EPIC-B is a National Cancer Research Network badged single arm, multi-center phase II trial, in treatment naïve locally advanced/metastatic penile cancer.
The key inclusion criteria were:
- Patient with locally advanced or metastatic carcinoma of the penis: TXN3MO or TXN2MO or T3N1MO or T4anyN or M1
- No previous chemotherapy for treatment of penile cancer
- Histologically proven squamous cell carcinoma of penis or penile urethra
- ECOG performance status 0, 1 or 2
- Adequate renal, liver and bone marrow function
- Measurable disease as per RECIST 1.1
Patients received cemiplimab 350mg IV D1 every 3 weeks (Q3W) up to a total of 34 cycles. The primary end point was investigator assessed Clinical Benefit Rate (CBR) at 12 weeks using RECIST 1.1. Secondary end points were safety; CBR at 1, 2, 3 years; Overall response rate (ORR); Progression free survival (PFS); Overall Survival (OS) and Quality of Life (QoL).
The study was designed with a significance level (α) of 0.05 and a power (1-β) of 0.8, assuming that a 5% primary endpoint response rate (p0=0.05) would indicate poor treatment efficacy, while a 25% response rate (p1=0.25) would be considered promising. Accounting for a 10% dropout rate, a total of 18 patients were recruited to test this hypothesis.
A total of 18 patients were recruited from 11 UK sites between November 2021 and April 2024. The median age was 72 years (range 44-88). Patients with ECOG 0-2 were eligible, with the majority having ECOG 1 or 2 (0=5%, 1=56%, 2=39%). Metastatic disease was present in 83% of patients, with sites of metastases including bone (5.6%), liver (5.6%), and lung (33.3%). Notably, the median number of cemiplimab cycles received was 4, and the median follow-up was 5.5 months (IQR 2.3-8.1).
At 12 weeks, the clinical benefit rate (CBR) was 38.9% (95% CI 20.3%-61.4%), and the objective response rate (ORR) was 16.6% (95% CI 5.8%-39.2%), including 1 complete response (CR), 3 partial responses (PR), and 4 patients with stable disease (SD). Over the full course of treatment, 27.8% of patients demonstrated a response (ORR).
Median progression-free survival (PFS) was estimated at 2.4 months (95% CI 1.0-3.8), while median overall survival (OS) was 10.7 months (95% CI 6.2-15.3).
The swimmer's plot below illustrates the duration of response for the 18 patients, with a median follow-up time of 5.5 months.
Regarding the safety profile, adverse events (AEs) of any grade were reported in 31% of patients and were considered related to cemiplimab. A total of 75 AEs were documented, with a median of 3 (IQR 1-5) per patient. The most common AE was infection, and no grade 4 AEs were recorded. There was one grade 5 AE (toxic epidermal necrolysis) related to treatment. Four patients discontinued treatment due to toxicity, including two cases (11%) attributed to cemiplimab.
Dr. Challapalli concluded the poster presentation with the following key messages:
- The EPIC-B trial demonstrates the efficacy of cemiplimab monotherapy as a treatment for locally advanced or metastatic penile cancer (la/mPC).
- The trial met its primary endpoint, with a clinical benefit rate (CBR) of 38.9% at 12 weeks.
- No new safety signals were identified.
- These data support cemiplimab monotherapy as a new standard-of-care first-line treatment for patients with la/mPC who ineligible for chemotherapy are.
Presented by: Amarnath Challapalli MD, Clinical Oncologist at Bristol Cancer Institute, University Hospitals Bristol NHS Foundation. Bristol, United Kingdom.
Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
References:- Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-351. doi: 10.1056/NEJMoa1805131. Epub 2018 Jun 4. PMID: 29863979.