Dataset Information

Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study.

ABSTRACT:

Background

Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.

Methods

This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity.

Findings

We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs.

Interpretation

In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed.

Funding

Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.

SUBMITTER: Bai X

PROVIDER: S-EPMC10641479 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in <i>BRAF</i> V600-mutant stage III melanoma after definitive surgery: a multicenter, retrospective cohort study.

Bai Xue X Shaheen Ahmed A Grieco Charlotte C d'Arienzo Paolo D PD Mina Florentia F Czapla Juliane A JA Lawless Aleigha R AR Bongiovanni Eleonora E Santaniello Umberto U Zappi Helena H Dulak Dominika D Williamson Andrew A Lee Rebecca R Gupta Avinash A Li Caili C Si Lu L Ubaldi Martina M Yamazaki Naoya N Ogata Dai D Johnson Rebecca R Park Benjamin C BC Jung Seungyeon S Madonna Gabriele G Hochherz Juliane J Umeda Yoshiyasu Y Nakamura Yasuhiro Y Gebhardt Christoffer C Festino Lucia L Capone Mariaelena M Ascierto Paolo Antonio PA Johnson Douglas B DB Lo Serigne N SN Long Georgina V GV Menzies Alexander M AM Namikawa Kenjiro K Mandala Mario M Guo Jun J Lorigan Paul P Najjar Yana G YG Haydon Andrew A Quaglino Pietro P Boland Genevieve M GM Sullivan Ryan J RJ Furness Andrew J S AJS Plummer Ruth R Flaherty Keith T KT

EClinicalMedicine 20231031

<h4>Background</h4>Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III <i>BRAF</i> V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.<h4>Methods</h4>This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, a ...[more]

PMID: 37965433

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