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

March 8, 2022

Abstract

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.

Source:

Eggermont, A. M., Meshcheryakov, A., Atkinson, V., Blank, C. U., Mandalà, M., Long, G. V., Barrow, C., Di Giacomo, A. M., Stephens, R., Sandhu, S. K., Kudchadkar, R. R., Ortiz-Romero, P. L., Svane, I. M., Van Akkooi, A. C., Krepler, C., Ibrahim, N., Marreaud, S., Kicinski, M., Suciu, S., & Robert, C. (2021). Crossover and Rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-mg/keynote-054 phase 3 trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma. Journal of Clinical Oncology, 39(15_suppl), 9500–9500. https://doi.org/10.1200/jco.20... 

https://www.ejcancer.com/article/S0959-8049(21)00620-1/fulltext#relatedArticles