Three-years real-world evidence of adjuvant dabrafenib plus trametinib (DT) in patients with resected melanoma in Spain (GEM 1901 - DESCRIBE-AD)

ABSTRACT

Background: DT combination has shown efficacy in the adjuvant setting for BRAF-mutated melanoma (BMM) patients (pts) in clinical trials. Previous reports from DESCRIBE-AD resulted in promising overall survival (OS) rates at 12 months. Methods: An observational retrospective study was carried out in 25 GEM sites in Spain. Histologically confirmed and resected BMM pts previously treated with DT according to standard clinical practice in the adjuvant setting were included. Only surgical resection was allowed as a prior treatment to DT. DT discontinuation rate and time to treatment discontinuation were the primary objective. Secondary objectives included safety and efficacy of the combination. Here, we report 3-year results for OS. Results: From 10/2020 to 03/2021, 65 pts were included. Median age was 58 years, 55% were male and 60%, 25%, and 14% had an ECOG PS 0/1/Uk respectively, one patient presented ECOG 3. Allocation of stage IIIA, IIIB and IIIC according to TNM AJCC 7th edition was 29%, 26% and 32%, respectively. There were 3 pts diagnosed at stage I/II but considered of risk, and 2 pts with stage IV but completely resected, all considered for adjuvant DT. Ulceration was present in 40%, Breslow ≥2 mm in 71%, and nodes were microscopically and macroscopically affected in 39% and 22% of pts, respectively. Only 9.2% of pts discontinued DT prematurely due to toxicity and 21.2% had dose reductions to manage toxicity. After a median follow-up of 36.2 m (range 13-51.1), the overall OS rate at 3-years was 83.5% (95% CI 74.5-93.5). According to AJCC 7 stage at diagnosis, the 3-years OS rate was 95.2% (95% CI 86.6-100), 75% (56-100), and 76.8% (60.7-97.2) for stage I-II-IIIA, IIIB, and IIIC-IV respectively. Throughout the study period 11 (16.9%) pts died, of which 10 died due to disease progression and one due to COVID-19 infection. Conclusions: Adjuvant treatment with DT for melanoma achieved good treatment compliance and has proven efficacy in the real world. Adjuvant DT has a clinical impact in survival in line with previous clinical trial COMBI-AD. Editorial acknowledgement We acknowledge Mfar Clinical Research staff for their assistance in the development of this . Legal entity responsible for the study Grupo Español Multidisciplinar en Melanoma (GEM). Funding: Grupo Español Multidisciplinar en Melanoma (GEM) as Sponsor with Industry partner NOVARTIS. Disclosure P. Cerezuela-Fuentes Financial Interests, Personal, Other, Consultancy, conference,congress attendance/infrastructure BMS, MSD, Pierre Fabre, Roche, Sanofi, SunPharma. J. Martín-Liberal Financial Interests, Personal, Other, Lecture fees Astellas, MSD;Financial Interests, Personal, Other, Lecture fees, advisory fees Bristol Myers Squibb, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi;Non-Financial Interests, Personal, Member, membership or affiliation ASCO, ESMO, SEOM, GEM, EORTC, SOGUG, GEIS. L.A. Fernández-Morales Financial Interests, Personal, Invited Speaker, Speak at sponsored meetings BMS, MSD, Pierre-Fabre, Roche;Financial Interests, Personal, Other, Speak at sponsored meetings and advisory role Novartis. J. Medina Martinez Financial Interests, Personal, Other, Speaker, consultancy or advisory role or similar activity Novartis, Roche, Pierre Fabre, BMS, MSD, Sanofi. M. Quindós Financial Interests, Personal, Other, speaker, consultancy and advisory AstraZeneca, GSK, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, Bristol Myers Squibb, Pierre Fabre;Financial Interests, Institutional, Other, Clinical trials Merck Sharp & Dohme, Roche, Bristol Myers Squibb. A. García Castaño Non-Financial Interests, Advisory Role Bristol, MSD, Novartis. T. Puértolas Financial Interests, Personal, Invited Speaker, Speaker and advisory role BMS, Novartis;Financial Interests, Personal, Invited Speaker Roche, MSD, Sun-Pharma;Financial Interests, Personal, Other, Speaker and advisory role Pierre-Fabre;Financial Interests, Personal, Advisory Role Sanofi;Financial Interests, Institutional, Other, Clinical trial Roche, BMS, Apexi en Inc, Aduro Biotech, Alkermes Inc;Non-Financial Interests, Institutional, Other, congresses inscriptions Lilly, Sun-Pharma, Novartis, Roche, MSD;Non-Financial Interests, Institutional, Leadership Role, Vocal GEM (Grupo Español Multidisciplinar de Melanoma);Non-Financial Interests, Institutional, Affiliate SEOM (Sociedad Española de Oncología Médica), GEM (Grupo Español Multidisciplinar de Melanoma). P. Ayala de Miguel Financial Interests, Personal, Invited Speaker, Public speaking Novartis, Merck Sharp & Dohme, Sanofi, Pierre-Fabré. B. Campos Financial Interests, Personal, Other, Speaker or advisory role Roche, BMS, Sanofi, Novartis, Pierre-Fabre, Sun Pharma;Financial Interests, Personal, Other, Speaker role AstraZeneca, Merck, ROVI, Leo Pharma. E. Espinosa Financial Interests, Personal, Advisory Role, Advisory BMS, MSD;Financial Interests, Personal, Other, Advisory, educational activities Novartis;Financial Interests, Personal, Invited Speaker, Advisory, educational activities Pierre Fabre;Financial Interests, Personal, Funding, Funding for translational investigation Roche;Non-Financial Interests, Personal, Member, Vicepresident Grupo Español Multidisciplinario de Melanoma. A. Rodríguez-Lescure Financial Interests, Personal, Advisory Role Pfizer, Novartis, ROCHE, AstraZeneca, Daiichi Sankyo, Seagen;Financial Interests, Personal, Invited Speaker, Public speaking Pierre-Fabre;Financial Interests, Institutional, Research Grant, Grant for Clinical Trials BMS, Lilly, Roche, Novartis, Amgen, Pzifer, Zimeworks, AstraZeneca, G1 Therapeutics, Bayer. L. Espasa Font Financial Interests, Personal, Full or part-time Employment Novartis. G. Belaustegui Ferrández Financial Interests, Personal, Full or part-time Employment Novartis. All other authors have declared no conflicts of interest.