This retrospective, observational, non-interventional cohort study aimed to assess OS in patients with advanced BRAFmt melanoma who received checkpoint inhibitors (CPI) and/or BRAF-MEK TT as first- (1L) and second-line (2L) treatment and the impact of treatment sequence (TxS).
Patients diagnosed with advanced BRAFmt melanoma between Jan, 2011 and June, 2020 in the nationwide Flatiron Health electronic health record-derived de-identified database were included if they were ≥18 years, treated after January 2015 with 1L CPI (ipilimumab, nivolumab or pembrolizumab) or 1L TT (dabrafenib/trametinib, binimetinib/encorafenib or cobimetinib/vemurafenib), had 6 months follow-up and had 2 visits before starting 1L therapy. Cox proportional hazard models adjusted for baseline confounders were used to investigate the association of OS with type of treatment.
A total of 853 patients were included in the analysis with 553 (64.8%)/300 (35.2%) and 155 (54%)/132 (46%) patients receiving CPI and TT, respectively in 1L and 2L. Median (CI) time to next treatment was 9.7 (7.5-13.0) and 7.2 (6.0-8.4) months for patients receiving CPI and TT in 1L, respectively. No statistically significant difference in OS was observed between those treated with TT as compared with CPI in 1L (HR: 1.17; CI: 0.90-1.56) and 2L (HR: 1.00; CI: 0.61-1.79) after adjusting for age, region, practice type, year of initial diagnosis, lactate dehydrogenase, albumin, Eastern Cooperative Oncology Group performance status, number of metastases and presence of brain and/or liver metastases. For patients receiving both CPI and TT sequentially, median (CI) OS was 21.5 (16.2-25.8) months for the CPI>TT cohort (n=123) and 18.2 (13.8-25.1) months for the TT>CPI cohort (n=115).
In the absence of standardized treatment for patients with advanced BRAFmt melanoma, CPI and TT are the preferred options with more patients initiating treatment with CPI in the real-world setting. In patients requiring 2L therapy, OS outcomes seem comparable irrespective of TxS. Whether TT or CPI should be administered first to specific populations requires randomized prospective evaluation.
Support for third-party writing assistance, furnished by Denise Kenski, PhD, of Health Interactions, Inc, was provided by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
M.B. Atkins: Advisory/Consultancy: BMS, Merck, Novartis, Arrowhead, Pfizer, Genentech-Roche, Exelixis, Eisai, Aveo, ImmunoCore, Iovance, Surface, COTA, Idera, Agenus, Apexigen, TRV, Neoleuken, Adagene, Werewolf, Fathom, Pneuma, Leads, Pyxis Oncology, PACT, Elpis, X4Pharma; Research grant/Funding (institution): BMS, Merck, Pfizer; Shareholder/Stockholder/Stock options: Werewolf, Pyxis Oncology, Elpis. C. Julian: Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech, Inc. M.H. Secrest: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. J. Lee: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech, Inc. A.M. Abajo: Full/Part-time employment: F. Hoffmann-La Roche Ltd. E. McKenna: Full/Part-time employment: Genentech, Inc; Shareholder/Stockholder/Stock options: F. Hoffmann-La Roche Ltd.