Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase III trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma

Alexander MM Eggermont, Andrey Meshcheryakov, Victoria Atkinson, Christian U. Blank, Mario Mandala, Georgina V. Long, Catherine Barrow, Anna Maria Di Giacomo, Rosalie Fisher, Shahneen Sandhu, Ragini Kudchadkar, Pablo Luis Ortiz Romero, Inge Marie Svane, James Larkin, Susana Puig, Peter Hersey, Pietro Quaglino, Paola Queirolo, Daniil Stroyakovskiy, Lars BastholtPeter Mohr, Micaela Hernberg, Vanna Chiarion-Sileni, Matthew Strother, Axel Hauschild, Naoya Yamazaki, Alexander CJ van Akkooi, Paul Lorigan, Clemens Krepler, Nageatte Ibrahim, Sandrine Marreaud, Michal Kicinski, Stefan Suciu, Caroline Robert

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

4 Citaten (Scopus)

Samenvatting

Background: In the phase III double-blind European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 trial, pembrolizumab improved recurrence-free and distant metastasis-free survival in patients with stage III cutaneous melanoma with complete resection of lymph nodes. In the pembrolizumab group, the incidence of grade I–V and of grade III–V immune-related adverse events (irAEs) was 37% and 7%, respectively. Methods: Patients were randomised to receive intravenous (i.v.) pembrolizumab 200 mg (N = 514) or placebo (N = 505) every 3 weeks, up to 1 year. On recurrence, patients could enter part 2 of the study: pembrolizumab 200 mg i.v. every 3 weeks up to 2 years, for crossover (those who received placebo) or rechallenge (those who had recurrence ≥6 months after completing 1-year adjuvant pembrolizumab therapy). For these patients, we present the safety profile and efficacy outcomes. Results: At the clinical cut-off (16-Oct-2020), in the placebo group, 298 patients had a disease recurrence, in which 155 (52%) crossed over (‘crossover’). In the pembrolizumab group, 297 patients completed the 1-year treatment period; 47 had a recurrence ≥6 months later, in which 20 (43%) entered the rechallenge part 2 (‘rechallenge’). In the crossover group, the median progression-free survival (PFS) was 8.5 months (95% confidence interval [CI] 5.7–15.2) and the 3-year PFS rate was 32% (95% CI 25–40%). Among 80 patients with stage IV evaluable disease, 31 (39%) had an objective response: 14 (18%) patients with complete response (CR) and 17 (21%) patients with partial response. The 2-year PFS rate from response was 69% (95% CI 48–83%). In the rechallenge group, the median PFS was 4.1 months (95% CI 2.6–NE). Among 9 patients with stage IV evaluable disease, 1 had an objective response (CR). Among the 175 patients, 51 (29%) had a grade I–IV irAE and 11 (6%) had a grade III–IV irAE. Conclusions: Pembrolizumab treatment after crossover yielded an overall 3-year PFS rate of 32% and a 39% ORR in evaluable patients, but the efficacy (11% ORR) was lower in those rechallenged.

Originele taal-2Engels
Pagina's (van-tot)156-168
Aantal pagina's13
TijdschriftEuropean Journal of Cancer
Volume158
DOI's
StatusGepubliceerd - nov. 2021

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