Efficacy and safety of 'Second Adjuvant' therapy with BRAF/MEK inhibitors after local therapy for recurrent melanoma following adjuvant PD-1 based immunotherapy.

Details

Serval ID
serval:BIB_CB58FC4C5C60
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Efficacy and safety of 'Second Adjuvant' therapy with BRAF/MEK inhibitors after local therapy for recurrent melanoma following adjuvant PD-1 based immunotherapy.
Journal
European journal of cancer
Author(s)
Taylor A.M., McKeown J., Dimitriou F., Jacques S.K., Zimmer L., Allayous C., Yeoh H.L., Haydon A., Ressler J.M., Galea C., Woodford R., Kahler K., Hauschild A., Festino L., Hoeller C., Schwarze J.K., Neyns B., Wicky A., Michielin O., Placzke J., Rutkowski P., Johnson D.B., Lebbe C., Dummer R., Ascierto P.A., Lo S., Long G.V., Carlino M.S., Menzies A.M.
ISSN
1879-0852 (Electronic)
ISSN-L
0959-8049
Publication state
Published
Issued date
03/2024
Peer-reviewed
Oui
Volume
199
Pages
113561
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Anti-PD-1 antibodies and BRAK/MEK inhibitors (BRAF/MEKi) reduce the risk of recurrence for patients with resected stage III melanoma. BRAFV600-mutated (BRAFmut) melanoma patients who recur with isolated disease following adjuvant therapy may be suitable for 'second adjuvant' treatment after local therapy. We sought to examine the efficacy and safety of 'second adjuvant' BRAF/MEKi.
Patients with BRAFmut melanoma treated with adjuvant PD-1 based immunotherapy who recurred, underwent definitive local therapy and were then treated with adjuvant BRAF/MEKi were identified retrospectively from 13 centres (second adjuvant group). Demographics, disease and treatment characteristics and outcome data were examined. Outcomes were compared to BRAFmut patients who did not receive 'second adjuvant' therapy (no second adjuvant group).
73 patients were included; 61 who received 'second adjuvant' therapy and 12 who did not. Most initially recurred on PD-1 therapy (66%). There were no differences in characteristics between groups. 92% of second adjuvant group received dabrafenib and trametinib and median duration of therapy was 11.8 months (0.4, 34.5). 72% required dose adjustments, 23% had grade 3 + toxicity and 38% permanently discontinued drug due to toxicity. After median 26.1 months (1.9, 56.3) follow-up, recurrence-free survival (RFS) was improved in second adjuvant group versus no second adjuvant group (median 30.8 vs 4 months, HR 0.35; p = 0.014), largely driven by a delay in early recurrence, with no difference in overall survival (p = 0.59).
This is the first study examining outcomes of 'second adjuvant' targeted therapy for melanoma, after failure of adjuvant PD-1 based immunotherapy. Data suggest a short-term improvement in RFS, but at the cost of toxicity. Alternative strategies and more data on sequencing adjuvant therapies are required to improve outcomes.
Keywords
Humans, Melanoma/drug therapy, Proto-Oncogene Proteins B-raf/genetics, Programmed Cell Death 1 Receptor/therapeutic use, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Skin Neoplasms/drug therapy, Adjuvants, Immunologic/therapeutic use, Immunotherapy, Mitogen-Activated Protein Kinase Kinases, Adjuvant, BRAF, Melanoma, PD-1, Recurrence, Targeted therapy
Pubmed
Create date
01/02/2024 16:45
Last modification date
27/02/2024 7:17
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