Treatment sequencing after adjuvant treatment failure in patients with melanoma: A retrospective cohort study.

Abstract

e21540 Background: Despite risk reduction for recurrence with adjuvant immune checkpoint inhibitors (ICI) and targeted therapy (TT) in resected stage IIB–III melanoma, the optimal treatment sequence in post-adj. relapse setting is unclear. Methods: Single-center retrospective cohort of pts with AJCC IIB–III cutaneous melanoma who relapsed after starting adj. treatment. The objective was to characterize treatment patterns of post-adj. relapse and to examine how treatment sequencing affects survival. Outcomes measured were recurrence-free survival 2 (RFS2), progression-free (PFS), time to second progression/relapse after adj. treatment start (TTSP) and overall survival (OS). RFS2 was time from 1 st resectable relapse to 2 nd relapse. PFS was time from 1 st irresectable relapse after start of adj. therapy to 2 nd progression. Sequencing groups were ICI→ICI rechallenge (A), ICI→TT switch (B), TT→ICI switch (C) and TT→TT rechallenge (D). Prespecified subgroup analyses assessed relapse resectability, BRAF status and relapse ON or OFF adj. treatment. Results: 306 pts received adj. treatment, 243 pts with stage III, from which 126 BRAF mut tumors, and 63 pts stage II. 88 pts recurred, 57 ON and 31 OFF adj. treatment, and 78/88 were treated with ICIs. 43/88 pts developed resectable relapse and 41 received a second adj systemic treatment (Table). 16/41 subsequently relapsed, but neither adj. treatment-related factors (type of adj. treatment, site of relapse) nor sequencing strategy significantly affected RFS2. 45 pts with irresectable relapse received systemic therapy only, 29 in group A, 11 in group B and 5 in group C. In 5/29 pts in group A second-line was anti-PD1 mono and in 24/29 anti-PD1+anti-CTLA4. In pts with BRAF mut tumors, treatment switch from ICI to TT derived better PFS than rechallenge. Finally, pts with irresectable relapse occurring during ICI adj. treatment demonstrated prolonged TTSP when subsequent treatment was TT, but not ICI rechallenge. Median OS was not reached for the total cohort. Conclusions: Relapse ON or OFF adj. treatment, type of relapse and subsequent treatment (ICI or TT) deemed significant predictors. Treatment switch after progression under ICI may improve survival of pts with BRAF mut melanoma and adverse prognostic features, such as early and irresectable relapse, possibly informing future therapeutic decision-making. RFS2 and PFS in pts with relapse after adj. treatment start and treatment sequencing from adj. to post-relapse setting. Resectable Irresectable Pts (n) / Events (n) (%) p-value Pts (n) / Events (n) (%) p-value Total 41 / 16 45 / 29 Treatment Sequencing ICI → ICI 20* / 8 (40) 0.610 29 / 21 (72.4) 0.06 ICI → TT 16 / 5 (31.3) 11 / 4 (36.4) TT → ICI 4 / 3 (75) 5 / 4 (80) TT → TT 1 / 0 (0) - Class of subsequent treatment post-adjuvant relapse Switch 20 / 8 (40) 0.852 16 / 8 (50) 0.05 Rechallenge 21 / 8 (38.1) 29 / 21 (72.4) *19 pts subsequent anti-PD1 mono and 1 anti-CTLA4. P-value from log-rank test.