(UroToday.com)The 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023 was host to a urothelial and other cancers abstract poster session. Dr. Elodie Coquan presented the results of a subgroup analysis of the phase II PEVOsq basket trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma of the penis.
Advanced penile squamous cell carcinoma remains a rare malignancy, with an estimated 36,068 incident cases in 2020. Treatment options remain limited for patients with advanced disease, particularly for those who progress on 1st line systemic therapy, and prognosis remains poor. Although PD-1 blockade appears to demonstrate some activity for patients with penile squamous cell carcinoma, response rates remain modest. There is evidence from pre-clinical data that vorinostat, an histone deacetylase (HDAC) inhibitor, might improve immunotherapy efficacy via epigenome modulation.
PEVOsq is an open-label, non-randomized, multi-center, basket phase II trial, evaluating the efficacy of pembrolizumab in combination with vorinostat in patients with recurrent and/or metastatic squamous carcinomas. Eligible patients had to be PD-1/L-1 inhibitor-naïve with no restrictions with regards to prior lines of treatment. Treatment dosages were as follows:
- Pembrolizumab: 200 mg intravenously every 3 weeks
- Vorinostat: 400 mg orally once daily
Sample size was determined using an A’Hern design assuming a type 1 (alpha) error rate of 10%, 85% power, and null and expected objective response rate (ORR) proportions of 5% and 30%. The primary outcome was ORR, per RECIST 1.1, with secondary endpoints of safety, progression-free survival, overall survival, and duration of reponse.
Among 112 patients in the basket trial, 11 patients with penile cancer were evaluated for safety and efficacy outcomes.
The median age was 71 years (range: 39 to 82). The median number of prior treatment lines was 1 (range: 0 to 2). An ORR was recorded in 2 patients (18.2%).
The median PFS and OS were 2.4 (95% CI: 0.5 – 4.1) and 4.4 (95% CI: 1.6 – 11.0) months, respectively.
Grade 3-4 adverse events occurred in 5 (45.5%) patients. Pembrolizumab and vorinostat were stopped for toxicity in 10% and 27.3% of patients, respectively. 54.5% of patients required a vorinostat dose reduction for toxicity, including hematologic and gastrointestinal toxicity, asthenia, and creatinine increase.
Dr. Coquan concluded that pembrolizumab combined with vorinostat produces limited efficacy in patients with advanced penile squamous cell cancer and was associated with a significant adverse event profile.
Presented by: Elodie Coquan, MD, Medical Oncology Department, Comprehensive Cancer Center Institute François Baclesse (CFB), Caen, France
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Congress held in Madrid, Spain between October 20th and 24th, 2023