TY - JOUR
T1 - 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
AU - Eggermont, Alexander Mm
AU - Meshcheryakov, Andrey
AU - Atkinson, Victoria
AU - Blank, Christian U
AU - Mandala, Mario
AU - Long, Georgina V
AU - Barrow, Catherine
AU - Di Giacomo, Anna Maria
AU - Fisher, Rosalie
AU - Sandhu, Shahneen
AU - Kudchadkar, Ragini
AU - Ortiz Romero, Pablo Luis
AU - Svane, Inge Marie
AU - Larkin, James
AU - Puig, Susana
AU - Hersey, Peter
AU - Quaglino, Pietro
AU - Queirolo, Paola
AU - Stroyakovskiy, Daniil
AU - Bastholt, Lars
AU - Mohr, Peter
AU - Hernberg, Micaela
AU - Chiarion-Sileni, Vanna
AU - Strother, Matthew
AU - Hauschild, Axel
AU - Yamazaki, Naoya
AU - van Akkooi, Alexander Cj
AU - Lorigan, Paul
AU - Krepler, Clemens
AU - Ibrahim, Nageatte
AU - Marreaud, Sandrine
AU - Kicinski, Michal
AU - Suciu, Stefan
AU - Robert, Caroline
N1 - Funding Information:
This work was supported by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc. , Kenilworth, NJ, USA.
Funding Information:
M.K.—study funding from Merck to institution; grants or contacts: Pierre Fabre; sponsor and provider of an academic grant for different melanoma studies (money paid to the author’s institution); BMS Sponsor and provider of an academic grant for different melanoma studies (money paid to the author’s institution).
Publisher Copyright:
© 2021 The Authors
PY - 2021/11/1
Y1 - 2021/11/1
N2 - 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.
AB - 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.
KW - Melanoma
KW - Pembrolizumab
KW - Salvage treatment
KW - anti–PD-1
U2 - 10.1016/j.ejca.2021.09.023
DO - 10.1016/j.ejca.2021.09.023
M3 - Article
C2 - 34678677
SN - 0959-8049
VL - 158
SP - 156
EP - 168
JO - European journal of cancer (Oxford, England : 1990)
JF - European journal of cancer (Oxford, England : 1990)
ER -
