How to help Patients deal with treatments in the New Melanoma era

commonly underrepresented in clinical trials.We therefore examined adjuvant TT toxicity and efficacy in older vs. younger pts.Methods: Pts with stage III, BRAF mutant melanoma who received adjuvant TT at The Christie (Jan 2019-Sep 2023), and Univ.Marq.de Valdecilla Hospital (UMVH) (Nov 2017-Dec 2022), were included in the initial cohort.Rates of toxicity (CTCAE v5 grading) and discontinuation due to toxicity were compared in patients <70 vs. 70 using chi-squared and relapse-free survival (RFS) was analysed using Kaplan-Meier and log-rank.Findings were validated in an international cohort of 14 centres.Results: Eighty-eight pts (IIIA n=15, IIIB n=22, IIIC n=49, IIID n=2), median age 55 yrs (23-83) n=68 <70, n=20 70, 50 pts male vs. 38 female received TT.Median follow-up was 40 months (95%CI 13-83).Rates of G1 toxicity were 66.2% (45/68) in <70 vs. 70% (14/20) in 70 pts (p=0.75);G2 toxicity was 44.1% (30/68) in <70 vs. 45% (9/20) in 70 pts (p=0.39).G3 toxicity was 13.2% (9/68) in <70 vs. 0% (0/20) in 70 pts (p=0.086);no G4 toxicity was observed.Discontinuation rates of TT due to toxicity were significantly higher in the 70 pts compared to <70 (60% vs 27%, p=0.018).RFS was significantly worse in 70 vs. <70 (median RFS 70 NR [95%CI 12-NR] vs. NR [95%CI NR] p=0.005).These findings were validated in a cohort of 366 pts (<70 n=308, 70 n=58) which showed inferior RFS and OS in pts 70 vs. <70 (median RFS 23.6 months [21.4-NR] vs. NR [42.6-NR]; p<0.001, median OS 48.7 months [39.6-NR] vs. NR [NR]; p=0.002 respectively) with a marginally higher treatment discontinuation due to toxicity (25.9% vs 14.9%, p= 0.06).Conclusions: Patients age 70 stage III melanoma treated with adjuvant TT had significantly worse RFS than those aged <70.The higher treatment discontinuation rate due to toxicity in patients 70 may have contributed to poorer outcomes.Age is therefore an important factor to consider in discussions regarding risk of toxicity and outcome to adjuvant targeted treatment.