EClinicalMedicine (Nov 2023)
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 studyResearch in context
- Xue Bai,
- Ahmed Shaheen,
- Charlotte Grieco,
- Paolo D. d’Arienzo,
- Florentia Mina,
- Juliane A. Czapla,
- Aleigha R. Lawless,
- Eleonora Bongiovanni,
- Umberto Santaniello,
- Helena Zappi,
- Dominika Dulak,
- Andrew Williamson,
- Rebecca Lee,
- Avinash Gupta,
- Caili Li,
- Lu Si,
- Martina Ubaldi,
- Naoya Yamazaki,
- Dai Ogata,
- Rebecca Johnson,
- Benjamin C. Park,
- Seungyeon Jung,
- Gabriele Madonna,
- Juliane Hochherz,
- Yoshiyasu Umeda,
- Yasuhiro Nakamura,
- Christoffer Gebhardt,
- Lucia Festino,
- Mariaelena Capone,
- Paolo Antonio Ascierto,
- Douglas B. Johnson,
- Serigne N. Lo,
- Georgina V. Long,
- Alexander M. Menzies,
- Kenjiro Namikawa,
- Mario Mandala,
- Jun Guo,
- Paul Lorigan,
- Yana G. Najjar,
- Andrew Haydon,
- Pietro Quaglino,
- Genevieve M. Boland,
- Ryan J. Sullivan,
- Andrew J.S. Furness,
- Ruth Plummer,
- Keith T. Flaherty
Affiliations
- Xue Bai
- Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China; Massachusetts General Hospital, USA; Corresponding author. Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
- Ahmed Shaheen
- Newcastle University Centre for Cancer, UK
- Charlotte Grieco
- Skin Unit, The Royal Marsden NHS Foundation Trust, London, UK
- Paolo D. d’Arienzo
- Skin Unit, The Royal Marsden NHS Foundation Trust, London, UK
- Florentia Mina
- Skin Unit, The Royal Marsden NHS Foundation Trust, London, UK
- Juliane A. Czapla
- Massachusetts General Hospital, USA
- Aleigha R. Lawless
- Massachusetts General Hospital, USA
- Eleonora Bongiovanni
- Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, Italy
- Umberto Santaniello
- Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, Italy
- Helena Zappi
- Alfred Health, Australia
- Dominika Dulak
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
- Andrew Williamson
- The Christie NHS Foundation Trust, Manchester, UK
- Rebecca Lee
- Division of Cancer Sciences, University of Manchester and Christie NHS Foundation Trust, Manchester, UK
- Avinash Gupta
- The Christie NHS Foundation Trust, Manchester, UK
- Caili Li
- Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
- Lu Si
- Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
- Martina Ubaldi
- University of Perugia, Italy
- Naoya Yamazaki
- Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan
- Dai Ogata
- Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan
- Rebecca Johnson
- Melanoma Institute Australia, The University of Sydney; Faculty of Medicine and Health, The University of Sydney; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia
- Benjamin C. Park
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Seungyeon Jung
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Gabriele Madonna
- Department of Melanoma, Cancer Immunotherapy and Development Therapeutics - Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
- Juliane Hochherz
- Department of Dermatology, University Skin Cancer Center, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- Yoshiyasu Umeda
- Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan
- Yasuhiro Nakamura
- Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan
- Christoffer Gebhardt
- Department of Dermatology, University Skin Cancer Center, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
- Lucia Festino
- Department of Melanoma, Cancer Immunotherapy and Development Therapeutics - Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
- Mariaelena Capone
- Department of Melanoma, Cancer Immunotherapy and Development Therapeutics - Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
- Paolo Antonio Ascierto
- Department of Melanoma, Cancer Immunotherapy and Development Therapeutics - Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy
- Douglas B. Johnson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Serigne N. Lo
- Melanoma Institute Australia, The University of Sydney, North Sydney, NSW, Australia
- Georgina V. Long
- Melanoma Institute Australia, The University of Sydney; Faculty of Medicine and Health, The University of Sydney; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia
- Alexander M. Menzies
- Melanoma Institute Australia, The University of Sydney; Faculty of Medicine and Health, The University of Sydney; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, Australia
- Kenjiro Namikawa
- Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan
- Mario Mandala
- University of Perugia, Italy
- Jun Guo
- Department of Melanoma and Sarcoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China
- Paul Lorigan
- Division of Cancer Sciences, University of Manchester and Christie NHS Foundation Trust, Manchester, UK
- Yana G. Najjar
- UPMC Hillman Cancer Center, Pittsburgh, PA, USA
- Andrew Haydon
- Alfred Health, Australia
- Pietro Quaglino
- Dermatologic Clinic, Department of Medical Sciences, University of Turin Medical School, Italy
- Genevieve M. Boland
- Massachusetts General Hospital, USA
- Ryan J. Sullivan
- Massachusetts General Hospital, USA
- Andrew J.S. Furness
- Skin Unit, The Royal Marsden NHS Foundation Trust, London, UK
- Ruth Plummer
- Newcastle University Centre for Cancer, UK
- Keith T. Flaherty
- Massachusetts General Hospital, USA; Corresponding author.
- Journal volume & issue
-
Vol. 65
p. 102290
Abstract
Summary: 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.
