Keytruda (pembrolizumab) plus platinum-based chemotherapy was both safe and efficacious in treating penile squamous cell carcinoma (PSCC), according to findings from the phase 2 HERCULES trial presented at the 2024 American Society of Clinical Oncology Annual Meeting.
Dr. Fernando Cotait Maluf, of Hospital Beneficência Portuguesa de São Paulo and Hospital Israelita Albert Einstein, São Paulo, Brazil, presented the data at the conference. In the presentation, Maluf noted that PSCC has up to a 10 times higher incidence in low-income countries in Africa, Asia and Latin America.He added that advanced PSCC is a disease for which no improvements have been made of late, and prognosis is poor, with an overall survival (OS; time patients live before death of any cause) of approximately six to seven months.
“Platinum-based chemotherapy has been considered the standard of care. … Immune checkpoint inhibitors have been associated with efficacy in different tumor types, including HPV16-positive tumors, such as cervical and head and neck squamous cell carcinoma,”Maluf explained.
Maluf and his coauthors hypothesized that the addition of Keytruda to platinum-based chemotherapy for first-line treatment of advanced penile cancer would be safe and associated with improved outcomes for patients.
Eligible patients were required to have an ECOG performance status of 0 to 1 (meaning that they were able to perform all their daily tasks independently), have metastatic disease, locally advanced disease that is not eligble to curative-intent therapy, loco-regional recurrence (cancer that returned to or nearby the original site) that is not amenable to curative-intent therapy, and no prior exposure to chemotherapy for advanced disease. However, prior presurgical chemotherapy was allowed if disease progressed after 12 months.
A total of 37 patients were included in the study, of whom five (13.5%) had locally advanced disease and eight (21.6%) had loco-regional recurrence. Thirty-three patients were eligible for an analysis to determine how well the treatment regimen worked.
The main goal of the trial was confirmed overall response rate (ORR; percentage of patients whose disease shrinks or disappears), as determined by the investigators on the study. Secondary goals included confirmed ORR by experts not involved in the trial, progression-free survival (PFS; time patients live without disease worsening), OS, safety and analysis of how this research may be able to influence cancer care for this population.
Confirmed ORR by researchers was 39.4%. Of these, one was a complete response, meaning that all signs of cancer disappeared (3%), and 12 (36.4%) were partial responses, meaning that the cancer shrunk but was still detectable on follow-up tests.
Confirmed ORR by experts unaffiliated with the study was 42.4%. Clinical benefit rate (percentage of patients who experience a complete response, partial response or stable disease) by researchers more than 24 weeks was 45.5%.
Maluf reported that tumor shrinkage of any magnitude was seen in 75.8% of patients. After a median follow-up of 24 months, median duration of response was 5.9 months and median time to response was 1.4 months. Median PFS was 5.4 months, and median OS was 9.6 months.
“Our biomarker exploratory analysis showed a potential correlation between response with [tumor mutational burden] as well as HPV16 status,” Maluf reported.
Regarding treatment-related side effects, Maluf reported 19 side effects (51.4%) of grade 3 (moderate) or higher and noted that only six patients (16.2%) experienced neutropenia (decrease in a type of white blood cells). Two (5.4%) immune-related side effects of grade 3 or higher were observed.
“The HERCULES trial is the first trial to demonstrate the efficacy of immune checkpoint inhibitors in [patients with] advanced penile cancer with [a] manageable safety profile. We are proud to say that [Keytruda] plus platinum-based therapy is a new treatment option for [patients with] advanced penile cancer,” Maluf said in his concluding remarks.
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