Abstract
Background
Anti-PD-1 antibodies and BRAF/MEK inhibitors are the two main groups of systemic therapy in the treatment of BRAFV600-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 monotherapy vs. BRAF/MEK inhibitors in advanced BRAFV600-mutant melanoma patients.
Methods
We selected patients diagnosed between 2014 and 2017 with advanced melanoma and a known BRAFV600-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 BRAFV600-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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Change history
07 March 2022
A Correction to this paper has been published: https://doi.org/10.1038/s41416-022-01772-z
15 March 2021
A Correction to this paper has been published: https://doi.org/10.1038/s41416-021-01312-1
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Acknowledgements
We thank all physicians and data managers who registered the patient data in the Dutch Melanoma Treatment Registry.
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Contributions
J.B. performed the analyses and wrote the manuscript. M.W. was responsible for the study conception and design, analysis and interpretation of data and drafting of the manuscript. D.H. was responsible for the study conception and design, analysis and interpretation of data and drafting of the manuscript. W.B. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. J.H. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. C.B. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. M.A. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. F.B. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript, performed critical revision and final approval of the manuscript. J.G. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. G.H. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. E.K. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. D.P. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. R.R. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. K.S. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. A.T. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. A.V. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. G.V. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. M.B. performed data acquisition, study conception, helped with the analysis and interpretation of the data, drafted the manuscript and performed critical revision and final approval of the manuscript. A.E. was responsible for the study conception and design, analysis and interpretation of data and drafting of the manuscript.
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Ethics approval and consent to participate
In compliance with Dutch regulations, the DMTR was approved by a medical ethical committee (METC Leiden University Medical Center, 2013) and is not considered subject to the Medical Research Involving Human Subjects Act.
Data availability
The datasets generated during and/or analysed during the current study are not publicly available due to privacy regulations in the Netherlands but are available from the corresponding author on reasonable request.
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, GlaxoSmithKline, 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.
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The original online version of this article was revised: The authors have noticed an error in the Abstract.
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van Breeschoten, J., Wouters, M.W.J.M., Hilarius, D.L. et al. First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis. Br J Cancer 124, 1222–1230 (2021). https://doi.org/10.1038/s41416-020-01229-1
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DOI: https://doi.org/10.1038/s41416-020-01229-1
