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.
| Title: | 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. |
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| Authors: | Mortier L; Université Lille, CHRU Lille, 42 Rue Paul Duez, Lille, France. laurent.mortier@chru-lille.fr.; Villabona L; Karolinska University Hospital, Akademiska stråket 13, G4:04, 17176, Stockholm, Sweden.; Lawrence B; University of Auckland, 85 Park Rd, Auckland City Hospital 2 Park Rd, Auckland, New Zealand.; Arance A; Hospital Clinic Barcelona and IDIBAPS, C. de Villarroel, 170, Barcelona, Spain.; Butler MO; Departments of Medicine and Immunology, University of Toronto, 610 University Avenue, Toronto, ON, Canada.; Beylot-Barry M; Centre Hospitalier Universitaire de Bordeaux, INSERM 1312, 1 Rue Jean Burguet, Bordeaux, France.; Saiag P; Hôpital Ambroise Paré, APHP & EA4340, University of Versailles-SQY, and Paris-Saclay University, 9 Av. Charles de Gaulle, Boulogne-Billancourt, France.; Samimi M; University of Tours, France; ISP1282 INRA University of Tours, 60 Rue du Plat d'Étain, Tours, France.; Ascierto PA; Istituto Nazionale Tumori IRCCS Fondazione 'G. Pascale', Via Mariano Semmola, 53, Naples, Italy.; Spada F; Istituto Europeo di Oncologia (IEO) IRCCS, Via Giuseppe Ripamonti, 435, Milan, Italy.; De Pontville M; Centre Hospitalier Universitaire de Caen-Hôpital Côte de Nacre, Av. de la Côte de Nacre CS 30001, Caen, France.; Maio M; University of Siena and Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy.; Berrocal A; Hospital General Universitario de Valencia, Avda. Tres Cruces, 2, Valencia, Spain.; Espinosa E; Service of Oncology, Hospital Universitario La Paz, Universidad Autónoma de Madrid - CIBERONC, P. Castellana, 261-Madrid, Spain.; Capdevila J; Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Pg. de la Vall d'Hebron, 119, Barcelona, Spain.; Levin M; University of Gothenburg and Sahlgrenska University Hospital, Universitetsplatsen 1, Gothenburg, Sweden.; Das D; Merck & Co., Inc., 126 E. Lincoln Ave, Rahway, NJ, USA.; Krepler C; Merck & Co., Inc., 126 E. Lincoln Ave, Rahway, NJ, USA.; Grebennik D; Merck & Co., Inc., 126 E. Lincoln Ave, Rahway, NJ, USA.; Chiarion-Sileni V; Istituto Oncologico Veneto IOV-IRCCS, Via Gattamelata, 64, Padua, Italy. |
| Source: | American journal of clinical dermatology [Am J Clin Dermatol] 2024 Nov; Vol. 25 (6), pp. 987-996. Date of Electronic Publication: 2024 Oct 08. |
| Publication Type: | Journal Article; Clinical Trial, Phase III; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: Adis, Springer International Country of Publication: New Zealand NLM ID: 100895290 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1179-1888 (Electronic) Linking ISSN: 11750561 NLM ISO Abbreviation: Am J Clin Dermatol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Auckland : Adis, Springer International; Original Publication: Auckland ; Philadelphia : Adis International, c2000- |
| MeSH Terms: | Antibodies, Monoclonal, Humanized*/administration & dosage ; Antibodies, Monoclonal, Humanized*/adverse effects ; Antibodies, Monoclonal, Humanized*/therapeutic use ; Carcinoma, Merkel Cell*/drug therapy ; Carcinoma, Merkel Cell*/mortality ; Carcinoma, Merkel Cell*/pathology ; Skin Neoplasms*/drug therapy ; Skin Neoplasms*/pathology ; Skin Neoplasms*/mortality ; Neoplasm Recurrence, Local*/drug therapy ; Antineoplastic Agents, Immunological*/adverse effects ; Antineoplastic Agents, Immunological*/administration & dosage ; Antineoplastic Agents, Immunological*/therapeutic use ; Progression-Free Survival*; Humans ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over ; Treatment Outcome ; Response Evaluation Criteria in Solid Tumors ; Adult |
| 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.; (© 2024. The Author(s).) |
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| Molecular Sequence: | ClinicalTrials.gov NCT03783078 |
| Substance Nomenclature: | 0 (Antibodies, Monoclonal, Humanized); DPT0O3T46P (pembrolizumab); 0 (Antineoplastic Agents, Immunological) |
| Entry Date(s): | Date Created: 20241008 Date Completed: 20241025 Latest Revision: 20241218 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11511690 |
| DOI: | 10.1007/s40257-024-00885-w |
| PMID: | 39377880 |
| Database: | MEDLINE |
Journal Article; Clinical Trial, Phase III; Multicenter Study