Pembrolizumab for the First-Line Treatment of Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma: Results from the Single-Arm, Open-Label, Phase III KEYNOTE-913 Study
October 10, 2024
Journal
American Journal of Clinical Dermatology
Publication Date
October 10, 2024
Authors
Merkelcell.org Summary
Immunotherapy is a type of drug that boosts the immune system and can help fight against Merkel cell carcinoma (MCC). The KEYNOTE clinical trial tested one such drug called pembrolizumab (also known as Keytruda) to see if it is safe and effective for MCC. The trial included 55 participants who took pembrolizumab every 3 weeks for up to 2 years. After starting treatment, 49% of patients had their cancer get better, and 69% of those patients still had a positive response two years later. 24% of patients experienced severe side effects from the treatment, with the most common being fatigue and itchy skin. This trial supports existing evidence that immunotherapy is a relatively safe and effective treatment for managing MCC.
Abstract
Background: The phase III KEYNOTE-913 study was conducted to evaluate the efficacy and safety of pembrolizumab as first-line therapy in patients with advanced Merkel cell carcinoma (MCC).
Objective: The aim was to report results from the primary analysis of KEYNOTE-913.
Patients and methods: Patients with recurrent locally advanced or metastatic MCC received pembrolizumab 200 mg intravenously every 3 weeks for up to 35 treatments (~ 2 years). The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary end points were duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 by BICR, overall survival (OS), and safety and tolerability.
Results: Fifty-five patients were treated with pembrolizumab. The median time from first dose to data cutoff (February 15, 2024) was 50.3 months (range 38.7-59.4). The ORR was 49% (95% confidence interval [CI] 35-63), with 12 complete responses and 15 partial responses. The median DOR was 39.8 months (range 4.8-52.5+), and the 24-month DOR rate was 69%. The median PFS was 9.3 months (95% CI 3-26), and the 24-month PFS rate was 39%. The median OS was 24.3 months (95% CI 12.4 to not reached), and the 24-month OS rate was 51%. Any-grade treatment-related adverse events (AEs) occurred in 38 patients (69%); 13 patients (24%) experienced grade 3-5 AEs. The most common treatment-related AEs were fatigue (n = 12 [22%]), pruritus (n = 12 [22%]), and lipase increase (n = 10 [18%]). One patient died of treatment-related Guillain-Barré syndrome.
Conclusions: Pembrolizumab provided durable antitumor activity and promising survival and had a manageable safety profile in patients with recurrent locally advanced or metastatic MCC, supporting its use in this population.
Trial registration: Clinicaltrials.gov, NCT03783078.
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