dc.contributor.author | Eggermont, AM | |
dc.contributor.author | Meshcheryakov, A | |
dc.contributor.author | Atkinson, V | |
dc.contributor.author | Blank, CU | |
dc.contributor.author | Mandala, M | |
dc.contributor.author | Long, GV | |
dc.contributor.author | Barrow, C | |
dc.contributor.author | Di Giacomo, AM | |
dc.contributor.author | Fisher, R | |
dc.contributor.author | Sandhu, S | |
dc.contributor.author | Kudchadkar, R | |
dc.contributor.author | Ortiz Romero, PL | |
dc.contributor.author | Svane, IM | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Puig, S | |
dc.contributor.author | Hersey, P | |
dc.contributor.author | Quaglino, P | |
dc.contributor.author | Queirolo, P | |
dc.contributor.author | Stroyakovskiy, D | |
dc.contributor.author | Bastholt, L | |
dc.contributor.author | Mohr, P | |
dc.contributor.author | Hernberg, M | |
dc.contributor.author | Chiarion-Sileni, V | |
dc.contributor.author | Strother, M | |
dc.contributor.author | Hauschild, A | |
dc.contributor.author | Yamazaki, N | |
dc.contributor.author | van Akkooi, AC | |
dc.contributor.author | Lorigan, P | |
dc.contributor.author | Krepler, C | |
dc.contributor.author | Ibrahim, N | |
dc.contributor.author | Marreaud, S | |
dc.contributor.author | Kicinski, M | |
dc.contributor.author | Suciu, S | |
dc.contributor.author | Robert, C | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-08-22T11:06:58Z | |
dc.date.available | 2022-08-22T11:06:58Z | |
dc.date.issued | 2021-10-18 | |
dc.identifier | S0959-8049(21)00620-1 | |
dc.identifier.citation | European Journal of Cancer, 2021, 158 pp. 156 - 168 | |
dc.identifier.issn | 0959-8049 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5291 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.eissn | 1879-0852 | |
dc.identifier.doi | 10.1016/j.ejca.2021.09.023 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.format.extent | 156 - 168 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER SCI LTD | |
dc.relation.ispartof | European Journal of Cancer | |
dc.rights.uri | https://creativecommons.org/licenses/by-nd/4.0/ | |
dc.subject | Melanoma | |
dc.subject | Pembrolizumab | |
dc.subject | Salvage treatment | |
dc.subject | anti–PD-1 | |
dc.title | 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. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-09-28 | |
dc.date.updated | 2022-08-22T11:05:29Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.ejca.2021.09.023 | |
rioxxterms.licenseref.startdate | 2021-10-18 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/34678677 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.publication-status | Published online | |
pubs.volume | 158 | |
dc.contributor.icrauthor | Larkin, James | |
icr.provenance | Deposited by Mr Arek Surman on 2022-08-22. Deposit type is initial. No. of files: 1. Files: 1-s2.0-S0959804921006201-main.pdf | |