In a phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017) reported in the Journal of Clinical Oncology, Nghiem et al found that first-line pembrolizumab produced a high response rate in patients with advanced Merkel cell carcinoma.
In the multicenter trial, 50 adult patients who had received no prior systemic therapy for advanced disease received pembrolizumab at 2 mg/kg every 3 weeks for up to 2 years. Response was assessed using Response Evaluation Criteria in Solid Tumors, version 1.1. Patients had a median age of 70.5 years, and 64% had Merkel cell polyomavirus–positive tumors.
Median follow-up was 14.9 months (range = 0.4–36.4+ months). The objective response rate was 56%, with complete response in 24% of patients. An additional 5 patients (10%) had stable disease. Responses were observed in 59% of virus-positive and 53% of virus-negative patients.
Among the 28 responders, median response duration was not reached (range = 5.9–34.5+ months). Progression-free survival at 24 months was 48.3%, and median progression-free survival was 16.8 months. Overall survival at 24 months was 68.7%, with median survival not being reached. Tumor viral status was not associated with progression-free survival or overall survival.
Among patients with available programmed cell death ligand 1 (PD-L1) expression status (positive defined as ≥ 1%), response was observed in 14 of 23 patients with PD-L1–positive tumor cells vs 13 of 23 patients with PD-L1–negative tumor cells (P = 1.0) and in 24 of 41 patients with PD-L1–positive immune cells vs 3 of 6 patients with PD-L1–negative immune cells (P = .68). A nonsignificant trend toward improved progression-free survival (P =.128) and overall survival (P = .057) was observed among patients with PD-L1–positve tumor cells.
Treatment-related grade ≥ 3 adverse events occurred in 14 patients (28%). Treatment-related adverse events led to discontinuation of treatment in 7 patients (14%). One treatment-related death was observed. The most common immune-mediated adverse events were hypothyroidism (6%) and pneumonitis (6%).
The investigators concluded, “Here, we present the longest observation to date of patients with [advanced Merkel cell carcinoma] receiving first-line anti–programmed cell death 1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable [overall survival] compared with historical data from patients treated with first-line chemotherapy.”
Paul Nghiem, MD, PhD, of the Department of Dermatology/Medicine, University of Washington, Seattle, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute, the Merkel cell carcinoma patient gift fund at University of Washington, the Kelsey Dickson MCC Challenge Grant from the Prostate Cancer Foundation, and Merck. The study authors' full disclosures can be found at jco.ascopubs.org.
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