1091P - Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant checkpoint inhibitor and subsequent surgical resection in patients with BRAF V600-mutated stage III/IV melanoma

Background

In BRAF mutant resected melanoma, both targeted therapy and immunotherapy have shown durable clinical benefit as 1^st line (1L) adjuvant therapy. However, there are no clinical studies evaluating 2^nd line (2L) adjuvant targeted therapy in patients with locoregional relapse and complete surgical resection following initial adjuvant immunotherapy.

Methods

This was a retrospective, multicenter chart review study of BRAF V600-mutated stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant checkpoint inhibitor therapy, then relapsed locoregionally or distantly, were again resected to NED, and then treated with dabrafenib/trametinib (dab/tram) as 2L adjuvant therapy. The primary endpoint was relapse-free survival (RFS-2) after initiation of dab/tram therapy. Secondary endpoints included overall survival (OS) and distant metastasis-free survival (DMFS). Analyses were descriptive with event time endpoints (RFS-2, OS, DMFS) estimated using the Kaplan-Meier method.

Results

A total of 37 patients were included (median age 51 years, 62% male, 89% stage III, median follow-up of 19 months from dab/tram initiation). Median time to dab/tram initiation after repeat resection to NED was 0.9 months (range: 0.2 – 2.8 months). A majority (73%) had discontinued dab/tram by last follow-up, with median therapy duration of 10.1 months (range: 1 day – 22.7 months). Median (95% confidence interval [CI]) RFS-2 was 18.9 (14.9 – 28.1) months, with 91% and 81% remaining relapse-free at 12 and 18 months, respectively; most patients also remained distant metastasis-free at 6 months (97%) and 12 months (85%). Only 2 patients were deceased at last follow-up, with nearly all patients (97%) still alive at 18 months; median OS was not reached.

Conclusions

More than 80% of patients remained relapse- and metastasis-free for at least 12 months after initiation of dab/tram. Longer follow-up and a larger patient cohort is needed in future studies to confirm efficacy of 2L adjuvant dab/tram in this population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Novartis.

Funding

Novartis.

Disclosure

J.S. Weber: Financial Interests, Personal, Advisory Board, Ad Boards: BMS; Financial Interests, Personal, Advisory Board: Merck, GSK, Incyte, Genentech, Pfizer, Biond, OncoC4, AstraZeneca, Regeneron, ImCheck, Novartis; Financial Interests, Personal, Stocks/Shares: Biond, Evaxion, Instil Bio, OncoC4; Financial Interests, Personal, Royalties: Moffitt Cancer Center; Financial Interests, Institutional, Local PI: BMS, Regeneron; Financial Interests, Institutional, Coordinating PI: Merck, Novartis; Non-Financial Interests, Principal Investigator: Moderna, BMS; Non-Financial Interests, Member: ASCO. S.N. Markovic: Financial Interests, Institutional, Royalties: Sorrento; Financial Interests, Institutional, Research Grant: Sorrento; Non-Financial Interests, Institutional, Research Grant: BMS; Non-Financial Interests, Institutional, Local PI: BMS. A.K.S. Salama: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Iovance, Regeneron, Replimune, Novartis, Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Ascentage, IDEAYA, Immunocore, Merck, Olatec, Regeneron, Replimune, Seagen. I. Mehmi: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: AstraZeneca. R.J. Sullivan: Financial Interests, Personal, Advisory Board: Merck, Novartis, Bristol Myers Squibb, Eisai, Iovance, OncoSec, Pfizer, Replimune, Marengo; Financial Interests, Personal, Royalties: Up-To-Date; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Invited Speaker: GSK, Pfizer, Sanofi, Moderna, Roche-Genentech, BioMed Valley Discoveries, Astex, Compugen, Beigene, Novartis, Rubius, Alkermes, Simcha Therapeutics, OnKure, Marengo, Synthekine. Y.G. Najjar: Financial Interests, Personal, Advisory Board: Immunocore, InterVenn Bio, Merck, BMS, Pfizer, Novartis; Financial Interests, Personal, Invited Speaker: Immunocore, Pfizer; Non-Financial Interests, Institutional, Funding: Merck, Pfizer, BMS, Replimune. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC, Provectus; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. A.M. Menzies: Financial Interests, Personal, Advisory Board, advisory board: BMS, MSD, Novartis, Roche, Pierre Fabre, QBiotics. G.V. Long: Other, Personal, Advisory Role: Agenus Inc., Amgen Inc., Array Biopharma, Boehringer Ingelheim, BMS, Evaxion Biotech, Hexal AG, Highlight Therapeutics, Innovent Biologics, MSD, Novartis Pharmaceuticals, OncoSec, PHMR, Pierre Fabre, Provectus, QBiotics, Regeneron. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharp & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharp & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Other, Editor-in-Chief IOTECH: ESMO; Other, Other, Editorial Board ESMO Open: ESMO; Other, Other, Editorial Board: Kidney Cancer. K. Davis: Financial Interests, Institutional, Funding: Novartis, AstraZeneca, Eisai, Gilead, Pfizer, Merck, Bristol Myers Squibb. S. Karanth: Financial Interests, Institutional, Funding, Full-time employee of RTI Health Solutions, an independent non-profit research organization, which was retained by Novartis to conduct the research that is being submitted to ESMO. Compensation is unconnected to the studies on which I work: Novartis; Financial Interests, Institutional, Funding, Full-time employee of RTI Health Solutions, an independent non-profit research organization, which was retained by Pfizer to conduct the research that is being submitted to ESMO. Compensation is unconnected to the studies on which I work: Pfizer. R. Shah: Financial Interests, Personal, Full or part-time Employment, Medical Director at Novartis: Novartis. L. Connolly: Financial Interests, Personal, Stocks/Shares: Novartis. D. Norton: Financial Interests, Institutional, Full or part-time Employment, work as head of Medical team for GI in the US: Novartis; Financial Interests, Institutional, Stocks/Shares, work as head of Medical team for GI in the US: Novartis; Financial Interests, Institutional, Funding, work as head of Medical team for GI in the US: Novartis; Non-Financial Interests, Leadership Role, work as head of Medical team for GI in the US: Novartis. All other authors have declared no conflicts of interest.