(LSM P4) Adjuvant Therapy Failure Patterns in the Post-MSLT-2 era

The MSLT-2 study demonstrated that active surveillance replace up-front completion lymphadenectomy in patients with stage III disease. Patterns of adjuvant failures have not been described in the post-MSLT-2 era, nor have immunotherapy versus targeted therapy outcomes been directly compared. Data from surgically-resected staged III/IV patients receiving anti-PD1, BRAF/MEKi, or surgical treatment only between July 2017 and September 2019 were analyzed. Primary endpoint was progression free survival. Secondary endpoints were location of recurrence, reason for therapy termination, and tumor characteristics. 40 patients received anti-PD1 therapy, 28 received BRAF/MEKi, and 18 surgery only. During a mean follow-up of 17 months, 25% patients in the anti-PD1 group developed recurrences, 11% in the BRAF/MEKi group, and 39% in the observation group. Progression free survival was 11.6 in anti-PD1, 11.4 months in the BRAF/MEKi, and 11.5 in the surgery group. Anti-PD1 termination occurred in 20 patients (50%), as a result of adverse events (n=12) and disease progression (n=8). Targeted therapy was discontinued 7 patients (25%) due to progression (n=2) and adverse events (n=7). Although our study is limited by lack of power, trends are detected. Early discontinuation due to toxicities was seen with both regimens (60% anti-PD1, 18% BRAF/MEKi). Anti-PD1 patients progressed early during therapy (4.4 months) compared to BRAF/MEK (8.2 months). Interestingly, anti-PD1 progressors were enriched in acral melanomas (33%). Targeted therapy progression was only seen in patients with high burden of disease (stage IIIC/IIID). Despite the small number, we are the first to comparatively characterize post-MSLT-2 adjuvant recurrences across treatment regimens.