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

Am J Clin Dermatol. 2024 Nov;25(6):987-996. doi: 10.1007/s40257-024-00885-w. Epub 2024 Oct 8.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Agents, Immunological* / administration & dosage
  • Antineoplastic Agents, Immunological* / adverse effects
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Carcinoma, Merkel Cell* / drug therapy
  • Carcinoma, Merkel Cell* / mortality
  • Carcinoma, Merkel Cell* / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / drug therapy
  • Progression-Free Survival*
  • Response Evaluation Criteria in Solid Tumors
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / mortality
  • Skin Neoplasms* / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • pembrolizumab
  • Antineoplastic Agents, Immunological

Associated data

  • ClinicalTrials.gov/NCT03783078