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Review
. 2023 Jul 25;15(15):3754.
doi: 10.3390/cancers15153754.

Efficacy and Safety of Rechallenge with BRAF/MEK Inhibitors in Advanced Melanoma Patients: A Systematic Review and Meta-Analysis

Jonathan N Priantti  1 , Maysa Vilbert  2   3 , Thiago Madeira  4 , Francisco Cezar A Moraes  5 , Erica C Koch Hein  2   3   6 , Anwaar Saeed  7 , Ludimila Cavalcante  8
Affiliations
Review

Efficacy and Safety of Rechallenge with BRAF/MEK Inhibitors in Advanced Melanoma Patients: A Systematic Review and Meta-Analysis

Jonathan N Priantti et al. Cancers (Basel). .

Abstract

This systematic review and meta-analysis aims to evaluate the efficacy and safety of rechallenging advanced melanoma patients with BRAFi/MEKi. Seven studies, accounting for 400 patients, were included. Most patients received immunotherapy before the rechallenge, and 79% underwent rechallenge with the combination of BRAFi/MEKi. We found a median progression-free survival of 5 months and overall survival of 9.8 months. The one-year survival rate was 42.63%. Regarding response, ORR was 34% and DCR 65%. There were no new or unexpected safety concerns. Rechallenge with BRAFi/MEKi can improve outcomes in advanced melanoma patients with refractory disease. These findings have significant implications for clinical practice, particularly in the setting of progressive disease in later lines and limited treatment options.

Keywords: BRAF/MEK inhibitors; MAPK inhibitors; advanced melanoma; rechallenge; targeted therapy.

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Conflict of interest statement

The authors J.N.P., T.M., F.C.A.M. and M.V., declare no conflict of interest. E.C.K.H.: Consulting or Advisory Role (Novartis). Speaker’s Bureau (Novartis and MSD). Travel, Accommodation, and Expenses (Pfizer, Novartis, and Roche Pharma AG). Research Funding (Novartis, funding paid to Dr. Koch Hein Institution for support of a melanoma registry in Chile). L.C.: Employment (Actuate Therapeutics). Consulting or Advisory Role (Pliant Therapeutics, Janssen, and CDR-Life). Stock and Other Ownership Interests (Actuate Therapeutics). A.S. reports research grants (to institution) from AstraZeneca, Bristol Myers Squibb, Merck, Clovis, Exelixis, Actuate Therapeutics, Incyte Corporation, Daiichi Sankyo, Five prime therapeutics, Amgen, Innovent biologics, Dragonfly therapeutics, KAHR medical, and Biontech, and advisory board fees from AstraZeneca, Bristol Myers Squibb, Exelixis, Pfizer, and Daiichi Sankyo.

Figures

Figure 1
Figure 1
PRISMA flow diagram of the study screening and selection.
Figure 2
Figure 2
Summary of the treatments administered during the first targeted therapy (TT) exposure (A), during the interval period (B), and the TT rechallenge period (C). During the first TT, most patients (58%) received the combination of BRAFi plus MEKi, and 42% received BRAFi alone. A total of 83% of patients received immunotherapy during the interval treatment, whereas 10% were on a drug holiday. In the rechallenge setting, almost 80% of patients received the combination of BRAFi plus MEKi, while 21% were treated with BRAFi alone.
Figure 3
Figure 3
Forest plots showed an ORR of 34.25% (A), a DCR of 65.01% (B), and a 1-year OS rate of 42.63% (C) [60,61,62,63,64,65,66].
Figure 4
Figure 4
Subgroup analysis of DCR during targeted therapy (TT) rechallenges according to the median BRAFi/MEKi-free interval. Patients with a BRAFi/MEKi-free interval ≥6 months had a DCR of 68.3%, significantly higher than patients with a BRAFi/MEKi-free interval of <6 months, with a DCR of 56.2% (p < 0.01) [60,61,62,63,64,65,66].
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