Abstract
The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.
| Original language | English |
|---|---|
| Article number | 2312 |
| Journal | Cancers |
| Volume | 13 |
| Issue number | 10 |
| ISSN | 2072-6694 |
| DOIs | |
| Publication status | Published - 02.05.2021 |
Funding
Conflicts of Interest: H.S., M.H., M.S., M.F., F.B., J.K., A.K., M.W. declare no conflict of interest. P.M. declares research support from Bristol Myers Squibb, Merck Sharp & Dohme and Novartis; speakers and advisory board honoraria from Amgen, Almirall Hermal, Bristol Myers Squibb, GlaxoSmithKline, Merck Sharp & Dohme, Merck Serono, Novartis, Pierre Fabre, Roche and Sanofi, and travel support from Bristol Myers Squibb, and Merck Sharp & Dohme, Novartis, Pierre Fabre, Amgen and Roche. S.H. served in advisory boards of Pierre Fabre, MSD, BMS, Novartis and Sanofi and received research project funding from BMS and Novartis outside the submitted work. D.N. served as consultant and payed referee to MSD, BMS, Novartis, Roche, Almirall Hermal, Mylan and Sanofi outside the submitted work. S.U. declares research support from Bristol Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Novartis and Roche, and travel support from Bristol Myers Squibb, and Merck Sharp & Dohme. D.S. declares relevant Honoria outside of this work from Roche, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck-Serono, Sanofi, Regeneron, Array, Pierre-Fabre, Pfizer, 4SC, Helsinn, Philogen, InFlarX, Amgen, SunPharma, Ultimovacs and Sandoz. E.L. served as consultant and/or has received honoraria from Amgen, Actelion, Roche, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Janssen, Medac, Sanofi, Sunpharma and travel support from Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, Amgen, Pierre Fabre, Sunpharma and Novartis, outside the submitted work. L.Z. declares honoria from Roche, BMS, MSD, Novartis, Pierre Fabre, consultant or advisory role honoria from BMS, Novartis, Pierre Fabre, Sunpharma, Sanofi and MSD, research funding from Novartis and travel support from BMS, Pierre Fabre, Sanofi, Amgen, Novartis and Sunpharma. U.L. declares research support from Merck Sharp & Dome; speakers and advisory board Honoria from Merck Sharp & Dome, Novartis Sun Pharma, Almirall Hemal, Sanofi and Roche outside the submitted work. A.F. served as a consultant to Roche, Novartis, MSD, BMS, Pierre-Fabre; received travel support from Roche, Novartis, BMS, Pierre-Fabre, and received speaker fees from Roche, Novartis, BMS, MSD and CeGAT, and reports institutional research grants from BMS Stiftung Immunonkologie. R.H. declares speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche and SUN-Pharma outside the submitted work. C.P. received honoraria (speaker honoraria or honoraria as a consultant) and travel support from: Novartis, BMS, Roche, Merck Serono, MSD, Celgene, AbbVie, Amgen, SUNPHARMA, Allergy Therapeutics and LEO. J.U. declares research support from Novartis, speakers and advisory board Honoria from BMS, MSD, Novartis, Pierre Fabre, Roche, Sanofi and Sun Pharma, and travel support from BMS, Medac and Sun Pharma outside the submitted work. F.M. has received travel support or/and speaker’s fees or/and advisor’s honoraria by Novartis, Roche, BMS, MSD and Pierre Fabre and research funding from Novartis and Roche. D.D. declares speakers and advisory board Honoria and/or travel support from BMS, MSD, Novartis, Pierre Fabre and Roche outside the submitted work. K.C.K. has served as consultant or/and has received Honoria from Amgen, Roche, BMS, MSD, Pierre Fabre and Novartis, and received travel support from Amgen, MSD, BMS, Pierre Fabre, Medac and Novartis. M.K. declares research support from Roche, MSD, BMS, Lilly, Sun Pharma, Novartis and lecture Honoria from MSD, BMS, Roche, Sun pharma and Novartis outside the submitted work. P.T. declares speaker’s honoraria from BMS, Novartis, MSD, Pierre-Fabre, CureVac and Roche, consultant’s honoraria from BMS, Novartis, Pierre-Fabre, Merck Serono, Sanofi und Roche and travel support from BMS, Pierre-Fabre and Roche. F.Z. declares personal fees outside the submitted work from Bristol-Myers Squibb GmbH & Co KG, Munich; MSD SHARP & DOHME GmbH, Haar; Roche Pharma AG, Grenzach-Wyhlen; GlaxoSmithKline GmbH & Co KG, Munich; Sanofi-Aventis GmbH, Berlin; Novartis Pharma GmbH, Nürnberg. S.G. declares honoraria for advisory boards, oral presentations and travel expenses from Roche, Novartis, MSD, and BMS outside the submitted work. C.L. declares speakers, advisory board honoraria and travel support from Bristol Myers Squibb, Merck Sharp and Dohme, Merck Serono, Novartis, Roche, Pierre Fabre, Sun Pharma, Kiowa Kirin, Sanofi, Biontech, Almirall Hermal outside the submitted work. Funding: H.S. and M.H. are supported by an intramural research funding of the UMC Mainz. M.H. supported by the Clinician Scientist Fellowship “TransMed Jumpstart Program: 2019_A72” supported by the Else Kröner Fresenius Foundation.
