35 | Real-world outcomes of targeted therapy in stage IV melanoma after relapse on adjuvant dabrafenib and trametinib: insights from a single-center cohort

Background: Adjuvant dabrafenib and trametinib (DT) reduce relapse risk in stage III BRAF-mutant melanoma, but data on recurrence patterns and management after relapse remain scarce. We evaluated recurrence features and outcomes of subsequent therapies in a real-world cohort, focusing on the impact of prior adjuvant treatment on response to metastatic targeted therapy (TT).Methods: We retrospectively analyzed 51 stage III patients treated with adjuvant DT, assessing RFS, treatment duration, toxicity, and relapse patterns. Additionally, outcomes of 167 stage IV patients (158 treatment-naïve, 9 previously exposed) receiving TT were evaluated with a focus on RR and PFS.Results: In the adjuvant cohort median age was 60 years and there were 35% female. Six patients (11%) discontinued adjuvant therapy early due to toxicity. Fourteen patients (27%) relapsed—one during treatment and the remainder at a median of 6 months after completing DT; two were local recurrences. Among 12 relapsed stage IV patients, lungs are the most common relapse site (50%), followed by liver and skin (33%). First-line therapy consisted of PD-1 inhibitors (alone or in combination) in 50% of patients and TT in the remaining 50%. Six patients received second-line treatment, including TT in three cases. In adjuvant-exposed patients, TT achieved an ORR of 77% and a median PFS of 7 months, compared with an ORR of 88% and median PFS of 15 months in treatment-naïve patients (Figure 1).Conclusions: Consistent with previous reports, TT showed reduced ORR and significantly shorter PFS when administered at relapse following adjuvant DT. Standardized data collection and prospective studies are needed to clarify whether a minimum interval from completion of adjuvant therapy is required to restore treatment efficacy. Figure 1.