First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis
van Breeschoten, Jesper; Wouters, Michel W J M; Hilarius, Doranne L; Haanen, John B; Blank, Christian U; Aarts, Maureen J B; van den Berkmortel, Franchette W P J; de Groot, Jan-Willem B; Hospers, Geke A P; Kapiteijn, Ellen; Piersma, Djura; van Rijn, Roos S; Suijkerbuijk, Karijn P M; Blokx, Willeke A M; Tije, Bert-Jan J Ten; Veldt, Astrid A M van der; Vreugdenhil, Art; Boers-Sonderen, Marye J; van den Eertwegh, Alfonsus J M
(2021) British Journal of Cancer, volume 124, issue 7, pp. 1222 - 1230
(Article)
Abstract
Background: Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAF V600-mutant advanced melanoma. Until now, data are inconclusive on which therapy to use as first-line treatment. The aim of this study was to use propensity score matching to compare first-line anti-PD-1
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monotherapy vs. BRAF/MEK inhibitors in advanced BRAF V600-mutant melanoma patients. Methods: We selected patients diagnosed between 2014 and 2017 with advanced melanoma and a known BRAF V600-mutation treated with first-line BRAF/MEK inhibitors or anti-PD-1 antibodies, registered in the Dutch Melanoma Treatment Registry. Patients were matched based on their propensity scores using the nearest neighbour and the optimal matching method. Results: Between 2014 and 2017, a total of 330 and 254 advanced melanoma patients received BRAF/MEK inhibitors and anti-PD-1 monotherapy as first-line systemic therapy. In the matched cohort, patients receiving anti-PD-1 antibodies as a first-line treatment had a higher median and 2-year overall survival compared to patients treated with first-line BRAF/MEK inhibitors, 42.3 months (95% CI: 37.3-NE) vs. 19.8 months (95% CI: 16.7–24.3) and 65.4% (95% CI: 58.1–73.6) vs. 41.7% (95% CI: 34.2–51.0). Conclusions: Our data suggest that in the matched BRAF V600-mutant advanced melanoma patients, anti-PD-1 monotherapy is the preferred first-line treatment in patients with relatively favourable patient and tumour characteristics.
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Keywords: Oncology, Cancer Research, Journal Article
ISSN: 0007-0920
Publisher: Springer Nature
Note: Funding Information: Competing interests A.J.M.V.D.E has consulting/advisory relationships with BMS, Roche, MSD, and Novartis. He received a study grant from Roche. J.W.D.G. has received personal fees outside the submitted work from Bristol-Myers Squibb, Pierre Fabre, Servier, MSD, Novartis. GH consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis and has received research grants not related to this paper from Bristol-Myers Squibb, Seerave. E.K. has consultancy/ advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, Merck, Pierre Fabre, and received research grants not related to this paper from Bristol-Myers Squibb. K.P.M.S. has consulting/advisory relationships with BMS and MSD. She received honoraria from Novartis, Pierre Fabre, and Roche. A.V.D.V. has consultancy relationships with Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai. J.H. has advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics and has received research grants not related to this paper from Novartis, Bristol-Myers Squibb, MSD, Neon Therapeutics. C.U.B. has received commercial research grants from Novartis, Bristol-Myers Squibb, and NanoString; is a paid advisory board member for Bristol-Myers Squibb, MSD, Roche, Novartis, GlaxoSmithK-line, AstraZeneca, Pfizer, Lilly, GenMab, and Pierre Fabre; and holds ownership interest in Uniti Cars, Neon Therapeutics, and Forty Seven. M.J.B.S. has consultancy relationships with Pierre Fabre, MSD and Novartis. All grants were paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication. All remaining authors have declared no conflicts of interest Funding information For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organisation The Netherlands Organization for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis and Roche Pharma. Roche Pharma stopped funding in 2019 and Pierre Fabre started funding of the DMTR in 2019. For this work no funding was granted. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Cancer Research UK.
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