First-line BRAF/MEK inhibitors versus anti-PD-1 monotherapy in BRAFV600-mutant advanced melanoma patients: a propensity-matched survival analysis

• Published in: British journal of cancer Vol. 124; no. 7; pp. 1222 - 1230
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.03.2021; Nature Publishing Group
• Subjects: 631/67/1813/1634; 692/4028/67/1813/1634; 692/699/67/1813/1634; Antibodies; Biomedical and Life Sciences; Biomedicine; Cancer Research; Diuretics; Drug Resistance; Epidemiology; MEK inhibitors; Melanoma; Molecular Medicine; Mutants; Oncology; PD-1 protein; Survival; Survival analysis; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-020-01229-1

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 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.