(UroToday.com) In this rapid abstract, Dr. Talal El Zarif and colleagues report on the safety and efficacy of immune checkpoint inhibitors (ICIs) in advanced penile carcinoma (PeCa), based on their multinational cohort derived from the Global Society of Rare Genitourinary Tumors (GSRGT).
As background, he noted that 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.
However, PeCa is rare in developed countries – but occurs as 10% of all male cancers in developing countries.
First line therapy for advanced PeCa remains platinum based chemotherapy (PBC). But, there are potential reasons why ICI may be attractive:
- Anecdotal evidence
- PD-L1 positivity is 32-67%
- Tumor Infiltrating Lymphocytes in 64-80%
- HPV positivity is 30-50%
- Many patients have contraindications for PBC
They retrospectively collected data on pts with biopsy proven advanced PeCa receiving ≥1 cycle of ICI between 2015-2022 at 18 medical centers in the US, Europe, and Asia. However, he pointed out on the map below that this is primarily in US and Europe, or developed Asian countries.
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.
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.
Among 37 pts with available data on HPV status, 24 (65%) were HPV+. 3 (4%) pts were HIV+.
Demographics summarized below:
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).
With regards to safety, 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.
Combination therapies were associated with increased TRAEs.
Looming at oncologic outcomes, 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.
Clinical outcomes reported stratified by the number of prior lines of therapy are:
ICI in the first line appears to have an improvement in mOS. But other parameters similar.
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.
HPV status was NOT a predictor of response (OS or PFS).
However, NLR>5 and absence of visceral metastases were associated with better OS:
Presented by: Talal El Zarif, MD, Dana-Farber Cancer Institute, Boston, MA
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.