The concepts of rechallenge and retreatment in melanoma: A proposal for consensus definitions.

Patients with BRAF-mutant melanoma commonly develop resistance to BRAF inhibitor and MEK inhibitor (BRAF/MEKi) treatment, resulting in disease recurrence or progression. Repeated treatment after a break or an intervening therapy may provide clinical benefit. To ensure a common understanding when discussing the treatment of BRAF-mutant melanoma, we propose consensus definitions for retreatment and rechallenge. 'Retreatment' should be defined as 'repeated treatment with the same therapeutic class following relapse after adjuvant treatment has ended.' Retreatment may be an option for patients with unresectable or metastatic disease who have completed prior adjuvant therapy or discontinued adjuvant therapy early due to toxicity or patients with locoregional recurrence after adjuvant treatment who subsequently underwent resection. 'Rechallenge' should be defined as 'repeated treatment with the same therapeutic class following disease progression in patients who had clinical benefit with prior treatment for unresectable or metastatic disease.' Rechallenge may be an option for patients who had disease progression after an initial response and received an alternative intervening treatment or patients with unresectable or metastatic melanoma who had a treatment break after responding to BRAF/MEKi therapy. Clinical benefits may be possible with repeated BRAF/MEKi treatment because of the role of the MAPK pathway in melanoma oncogenesis and resistance mechanisms specific to BRAF/MEKi, which are discussed in this article. The concepts of retreatment and rechallenge may also be relevant for treatment with immune checkpoint inhibitors in patients with melanoma. Use of consistent terminology will help to stimulate and align further research in this area.
Competing Interests: Conflict of interest statement P.A. reports a consultant/advisory role for Bristol Myers-Squibb (BMS), Roche-Genentech, Merck Sharp & Dohme (MSD), Array, Novartis, Merck Serono, Pierre Fabre, Incyte, NewLink Genetics, Genmab, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar and Boehringer-Ingelheim; receiving research funds from Bristol Myers-Squibb, Roche-Genentech and Array; and receiving travel support from MSD. V.A. reports receiving speaker/advisory board fees from BMS, MSD, Merck, Novartis, Roche, Pierre Fabre and NEKTAR therapeutics. P.C. reports receiving personal speaker/advisory board fees from BMS, Merck & Co, Novartis and Pierre Fabre. R.D. reports intermittent, project-focused consulting and/or advisory relationships with Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron and Alligator outside the submitted work. C.G. reports receiving personal speaker/advisory board fees from Amgen, Beiersdorf, BMS, MSD, Novartis, Pierre Fabre, Roche, Sun Pharma and Sanofi Genzyme. D.S. reports a consultant/advisory role in the last 2 years for Bristol Myers-Squibb (BMS), Roche-Genentech, Merck Sharp & Dohme (MSD), Array, Immunocore, InFlaRX, Nektar, Novartis, Merck Serono, Pierre Fabre, Pfizer, Philiogen, Regeneron, Sun Pharma, Sandoz, Sanofi, Ultimovacs and 4SC. D.S. also reports receiving research funds from Bristol Myers-Squibb, Roche, Amgen and Novartis.
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