Efficacy of rechallenge with BRAF inhibition therapy in patients with advanced BRAFV600 mutant melanoma
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The treatment of patients with BRAFv600 mutant melanomas progressing to BRAF inhibitors (BRAFi) and immunotherapy remains challenging. Preclinical studies and a small phase 2 trials have recently suggested that rechallenging with BRAFi may have a roll in these patients. The aim of this systematic review was to summarise the current evidence on the efficacy of BRAF inhibition therapy rechallenge after progression to BRAFi in metastatic BRAFv600 melanoma patients.
Materials and methods
We performed a systematic literature search in MEDLINE, Embase and the Cochrane Library CENTRAL up to November 2018. The target was restricted to patients with unresectable and/or metastatic BRAF V600 mutant melanoma that had previously progressed on BRAFi, were off-treatment for a period of time and then retreated with a BRAF inhibition strategy. We included prospective trials, observational studies and case reports. The primary outcomes were overall response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and median overall survival since the start of the treatment.
Up to November 2018, nine reports met our inclusion criteria: five case reports, three observational studies and a phase 2 trial. No comparative studies have been reported. In total, 188 patients met the inclusion criteria for this review. Efficacy results of the observational reports and the clinical trial are presented. ORR varied between 28 and 43% and DCR between 57 and 72%. Duration of response was reported in 1 retrospective study and was of 14 months. PFS varied between 4.9 and 5 months and OS was not reported in all studies.
Although no comparative studies have been conducted, rechallenging with BRAF inhibition therapy seems a plausible treatment option. Randomized trials are needed to confirm these results.
KeywordsMetastatic melanoma Treatment Rechallenge BRAF
This work has not been supported by public grants or financial support. No sources of funding were used to assist in the preparation of this manuscript.
All authors have contributed equally to this work. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
EE received honoraria for advisoring and conferences from Novartis, Roche and Pierre Fabre.
This article does not contain any studies with human participants or animals performed by any of the authors.
For this type of study, formal consent is not required.
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