In a Brazilian phase II trial (HERCULES; LACOG 0218) reported in JAMA Oncology, Maluf et al found that pembrolizumab plus platinum-based chemotherapy showed activity in patients with advanced penile squamous cell carcinoma. The investigators explained, “Advanced penile squamous cell carcinoma is associated with poor survival, and no new treatment strategies have changed clinical outcomes in past decades. This highlights the unmet need to understand the biology and develop more effective and tolerable treatment options.”
Study Details
In the multicenter trial, 37 patients enrolled between August 2020 and December 2022 received fluorouracil at 1,000 mg/m2 per day on days 1 to 4, cisplatin at 70 mg/m2 (or carboplatin AUC = 5) on day 1, and pembrolizumab at 200 mg on day 1 every 3 weeks for six cycles, followed by pembrolizumab at 200 mg every 3 weeks for up to 34 cycles. Patients had metastatic, recurrent, or locally advanced disease not amenable to curative-intent therapy. The primary outcome measure was objective response rate.
Key Findings
Among 33 evaluable patients, objective response was observed in 13 (39.4%, 95% confidence interval [CI] = 22.9%–57.9%), including complete response in 1 (3.0%). An additional seven patients (21.2%) had stable disease for at least 12 weeks. Median duration of response was 5.9 months (95% CI = 4.4–9.0 months). No difference in objective response rate was observed between PD-L1–positive vs PD-L1–negative patients.
At a median follow-up of 24.0 months (cutoff in January 2024), median progression-free survival was 5.4 months (95% CI = 2.7–7.2 months). Median overall survival was 9.6 months (95% CI = 6.4–13.2 months), with rates at 6, 12, and 24 months of 69.7%, 41.4%, and 19.4%, respectively.
Among all 37 patients, grade ≥ 3 adverse events occurred in 83.8%; the most common were neutropenia (21.6%), leukopenia (16.2%), anemia (10.8%), and hypercalcemia (10.8%). Immune-related adverse events of any grade occurred in 21.6% of patients, most commonly hypothyroidism (8.1%), and were grade ≥ 3 in 5.4%. No treatment-related deaths were reported.
The investigators concluded: “The HERCULES clinical trial is the first trial to demonstrate the efficacy of immune checkpoint inhibitors combined with chemotherapy in patients with advanced [penile squamous cell carcinoma] with a manageable safety profile.”
Fernando Cotait Maluf, PhD, of Latin American Cooperative Oncology Group (LACOG), Porto Alegre, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme, LLC. For full disclosures of all study authors, visit jamanetwork.com.
