Dr Maluf on Pembrolizumab Plus Platinum-Based Chemotherapy in Advanced Penile Cancer

Fernando C. Maluf, MD, PhD,chief, medical oncology, Beneficencia Portuguesa; member, steering committee, Medical Oncology Center, Albert Einstein Hospital, São Paulo, Brasil, discusses findings from the phase 2 HERCULES (NCT04224740) phase 2, single-arm study evaluating the efficacy of a combined regimen of cisplatin or carboplatinplatinum-based chemotherapy, 5-fluorouracil (5-FU), and pembrolizumab (Keytruda) in advanced penile squamous cell carcinoma (PSCC).

This study is significant given the limited treatment options and poor prognosis associated with advancedPatients with PSCC often experience poor prognosis and have limited treatment options. Accordingly, , where platinum-based chemotherapy has beencontinues to be the standard first-line treatment in this disease setting, Maluf begins.for six decades.

The study included 37 patients, with 33 of whom were evaluable for efficacy. Patients received six cycles of cisplatin or carboplatinon day 1 of treatment alongside 5-fluorouracil (5-FU) on days 1 and 4 plus pembrolizumabthe combination therapy every three 3 weeks for 6 cycles. Those with aPatients who achieved a response or stable disease continued on maintenance pembrolizumab for up to 34 cycles. The primary endpoint was confirmed overall response rate (ORR), confirmed by investigator assessment, with secondary endpoints including progression-free survival (PFS), overall survival (OS), safety, and translational research analyseis. The trial was conducted across 11 sites in Brazil.

The rResults presented at the 2024 ASCO Annual Meetingshowed a primary endpointaninvestigator-assessed ORR of 39.4% (95% CI, 22.9%-57.9%), confirmed by investigator assessment, and a slightly higher ORR of 42.4% (95% CI, 25.5%-60.8%)per blinded independent central review with the experimental regimenby central review. The duration of response was 5.9 months (95% CI, 4.4-9.0), and the time to response was 1.4 months (95% CI, 1.3-1.8). Notably, some patients exhibited long-term responses, which are uncommon with chemotherapy alone, Maluf adds.

Maluf nnoted otes that the regimen was well-tolerated, with no new safety signals compared tono new safety signals observed. other trials involving pembrolizumab and chemotherapy. Biomarker analysis indicated revealed a potential correlation between response anda correlation betweenthat HPV 16-positive tumors, as well aspositivity tumors withand high tumor mutational burden (TMB) may predict )responses withplatinum-based chemotherapy plus pembrolizumab. However, no correlation was found between response to treatment and PD-L1 status.

The HERCULES i trial is the first trial to demonstrate the efficacy of immune checkpoint inhibitors, specifically pembrolizumab, combined with platinum-based chemotherapy in advanced PSCC. It The regimen represents a promising potential new treatment option for patients with metastatic or locally advanced PSCC not who are not amenable to surgical intervention