Jesper van Breeschoten1,2, Michel W J M Wouters1,3, Doranne L Hilarius4, John B Haanen5, Christian U Blank5,6, Maureen J B Aarts7, Franchette W P J van den Berkmortel8, Jan-Willem B de Groot9, Geke A P Hospers10, Ellen Kapiteijn11, Djura Piersma12, Roos S van Rijn13, Karijn P M Suijkerbuijk14, Willeke A M Blokx15, Bert-Jan J Ten Tije16, Astrid A M van der Veldt17, Art Vreugdenhil18, Marye J Boers-Sonderen19, Alfonsus J M van den Eertwegh20. 1. Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden, 2333AA, The Netherlands. 2. Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, Amsterdam, 1081HZ, The Netherlands. 3. Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands. 4. Department of Pharmacy, Rode Kruis Ziekenhuis, Vondellaan 13, Beverwijk, 1942LE, The Netherlands. 5. Department of Medical Oncology and Immunology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands. 6. Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066CX, The Netherlands. 7. Department of Medical Oncology, Maastricht University Medical Centre, P. Debyelaan 25, Maastricht, 6229 HX, The Netherlands. 8. Department of Medical Oncology, Zuyderland Medical Centre Sittard, Dr. H. van der Hoffplein 1, Sittard-Geleen, 6162BG, The Netherlands. 9. Isala Oncology Center, Isala, Dokter van Heesweg 2, Zwolle, 8025AB, The Netherlands. 10. Department of Medical Oncology, University Medical Centre Groningen, Hanzeplein 1, Groningen, 9713GZ, The Netherlands. 11. Department of Medical Oncology, Leiden University Medical Centre, Albinusdreef 2, Leiden, 2333ZA, The Netherlands. 12. Department of Internal Medicine, Medisch Spectrum Twente, Koningsplein 1, Enschede, 7512KZ, The Netherlands. 13. Department of Internal Medicine, Medical Centre Leeuwarden, Henri Dunantweg 2, Leeuwarden, 8934AD, The Netherlands. 14. Department of Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht, 3584CX, The Netherlands. 15. Department of Pathology, Division of Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht. Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands. 16. Department of Internal Medicine, Amphia Hospital, Molengracht 21, Breda, 4818CK, The Netherlands. 17. Departments of Medical Oncology and Radiology & Nuclear Medicine, Erasmus Medical Centre, 's-Gravendijkwal 230, Rotterdam, 3015CE, The Netherlands. 18. Department of Internal Medicine, Maxima Medical Centre, De Run 4600, Eindhoven, 5504DB, The Netherlands. 19. Department of Medical Oncology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, Nijmegen, 6525GA, The Netherlands. 20. Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, Amsterdam, 1081HZ, The Netherlands. vandeneertwegh@amsterdamumc.nl.
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.
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.
Authors: Jacob Schachter; Antoni Ribas; Georgina V Long; Ana Arance; Jean-Jacques Grob; Laurent Mortier; Adil Daud; Matteo S Carlino; Catriona McNeil; Michal Lotem; James Larkin; Paul Lorigan; Bart Neyns; Christian Blank; Teresa M Petrella; Omid Hamid; Honghong Zhou; Scot Ebbinghaus; Nageatte Ibrahim; Caroline Robert Journal: Lancet Date: 2017-08-16 Impact factor: 79.321
Authors: Caroline Robert; Antoni Ribas; Jacob Schachter; Ana Arance; Jean-Jacques Grob; Laurent Mortier; Adil Daud; Matteo S Carlino; Catriona M McNeil; Michal Lotem; James M G Larkin; Paul Lorigan; Bart Neyns; Christian U Blank; Teresa M Petrella; Omid Hamid; Shu-Chih Su; Clemens Krepler; Nageatte Ibrahim; Georgina V Long Journal: Lancet Oncol Date: 2019-07-22 Impact factor: 41.316
Authors: Georgina V Long; Jean-Jacques Grob; Paul Nathan; Antoni Ribas; Caroline Robert; Dirk Schadendorf; Stephen R Lane; Carmen Mak; Philippe Legenne; Keith T Flaherty; Michael A Davies Journal: Lancet Oncol Date: 2016-11-16 Impact factor: 41.316