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Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma

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Titel: Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma
Autoren: Jeffrey Weber, Waqas Haque, Svetomir N Markovic, April K S Salama, Inderjit Mehmi, Ryan J Sullivan, Yana G Najjar, Alexander C J van Akkooi, Alexander M Menzies, Georgina V Long, Amelia M Taylor, John Haanen, Lisanne P Zijlker, Keith L Davis, Siddharth Karanth, Deborah Norton, Lucy Connolly
Quelle: Oncologist
The oncologist, vol. 30, no. 3
Verlagsinformationen: Oxford University Press (OUP), 2024.
Publikationsjahr: 2024
Schlagwörter: 03 medical and health sciences, 0302 clinical medicine, Humans, Oximes/administration & dosage, Oximes/therapeutic use, Oximes/pharmacology, Melanoma/drug therapy, Melanoma/genetics, Melanoma/pathology, Melanoma/mortality, Male, Female, Middle Aged, Imidazoles/therapeutic use, Imidazoles/administration & dosage, Imidazoles/pharmacology, Proto-Oncogene Proteins B-raf/genetics, Pyrimidinones/administration & dosage, Pyrimidinones/therapeutic use, Pyrimidinones/pharmacology, Pyridones/administration & dosage, Pyridones/therapeutic use, Pyridones/pharmacology, Retrospective Studies, Adult, Aged, Neoplasm Staging, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/pharmacology, Chemotherapy, Adjuvant/methods, Neoplasm Recurrence, Local/drug therapy, Neoplasm Recurrence, Local/pathology, Skin Neoplasms/drug therapy, Skin Neoplasms/pathology, Skin Neoplasms/genetics, Skin Neoplasms/mortality, Mutation, Disease-Free Survival, BRAF mutation, dabrafenib, melanoma, relapse-free survival, trametinib, Melanoma and Cutaneous Malignancies
Beschreibung: Background In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. Patients and methods This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of disease, and received dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy. The primary endpoint was relapse-free survival (RFS) from initiation of 2L adjuvant dab/tram (RFS-2), analyzed via Kaplan-Meier methods. Results Thirty-eight patients were included (median age 50 years, 63% male, 87% stage III, median follow-up 19 months from 2L dab/tram initiation). Median dab/tram duration was 10.1 months (range: 1 day–22.7 months), with half discontinuing due to progression or adverse events. Median (95% CI) RFS-2 was 18.9 (14.9–28.1) months, with 91%, 81%, and 58% remaining relapse-free at 6, 12, and 18 months, respectively. Most patients remained distant metastasis-free at 6, 12, and 18 months (97%, 85%, and 71%, respectively). Two patients were deceased at the last follow-up, with 97% alive at 18 months. Conclusions Over 80% of patients remained relapse- and metastasis-free at 12 months after 2L dab/tram initiation, with only 2 deaths observed. Dab/tram appears to have activity in the 2L adjuvant setting, although more follow-up is required.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1549-490X
1083-7159
DOI: 10.1093/oncolo/oyae289
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/39560953
https://serval.unil.ch/notice/serval:BIB_A8A26871D41B
http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_A8A26871D41B1
https://serval.unil.ch/resource/serval:BIB_A8A26871D41B.P001/REF.pdf
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Dokumentencode: edsair.doi.dedup.....cabe099c8bd2ed0f0db0686d977dc203
Datenbank: OpenAIRE
Beschreibung
Abstract:Background In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. Patients and methods This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of disease, and received dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy. The primary endpoint was relapse-free survival (RFS) from initiation of 2L adjuvant dab/tram (RFS-2), analyzed via Kaplan-Meier methods. Results Thirty-eight patients were included (median age 50 years, 63% male, 87% stage III, median follow-up 19 months from 2L dab/tram initiation). Median dab/tram duration was 10.1 months (range: 1 day–22.7 months), with half discontinuing due to progression or adverse events. Median (95% CI) RFS-2 was 18.9 (14.9–28.1) months, with 91%, 81%, and 58% remaining relapse-free at 6, 12, and 18 months, respectively. Most patients remained distant metastasis-free at 6, 12, and 18 months (97%, 85%, and 71%, respectively). Two patients were deceased at the last follow-up, with 97% alive at 18 months. Conclusions Over 80% of patients remained relapse- and metastasis-free at 12 months after 2L dab/tram initiation, with only 2 deaths observed. Dab/tram appears to have activity in the 2L adjuvant setting, although more follow-up is required.
ISSN:1549490X
10837159
DOI:10.1093/oncolo/oyae289