Conditional survival in advanced melanoma treated with immune checkpoint inhibitors.

Abstract

12108 Background: Immune checkpoint inhibitors (ICI) have improved survival in advanced melanoma, with some patients achieving durable remissions. Traditional survival estimates at diagnosis do not reflect how prognosis changes over time. Conditional survival (CS) provides a framework for time-dependent prognostication in long-term responders. Methods: We conducted a population-based retrospective cohort study of patients with unresectable/metastatic cutaneous melanoma treated with ≥1 dose of PD1-inhibitor based therapy in British Columbia (2012 -2022). Progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS) were estimated using Kaplan–Meier methods. Median follow-up was estimated using reverse Kaplan-Meier methods. Conditional PFS was calculated from ICI initiation and stratified by baseline characteristics and treatment response. Results: Among 897 patients, median age was 65 years (range 19-99); 48% (n=436) were M1c-d and 32% (n=290) received dual ICI. Median follow-up was 6.0 years (95% CI 5.7-6.3) and median OS was 3.2 years (95% CI 2.8-3.8); 5- and 10-year OS rates were 41% and 27%, respectively, while MSS rates were 49% and 38%, respectively. 5- and 10-year PFS rates were 31% and 22%, respectively. Conditional PFS analyses showed a decreasing risk of progression over time, most pronounced in patients achieving a complete response (Table 1). At 3-years post ICI initiation, patients in a complete response had a 5-year conditional PFS rate of 91% (95% CI 85-95%). Further analysis will assess whether their mortality normalizes relative to age- and sex-matched population controls to contextualize long-term survivorship. Conclusions: CS demonstrates dynamic improvement in prognosis among advanced melanoma patients who remain progression-free after ICI and provides clinically meaningful, time-updated prognostic information to guide patient counseling and follow-up strategies. Five-year conditional PFS rate at ICI initiation (year 0) and subsequent PFS timepoints. Strata (%; 95% CI) Year 0 Year 1 Year 2 Year 3 Year 4 All patients 31% (28-34%) 53% (48-57%) 67% (62-72%) 80% (75-84%) 90% (85-93%) ECOG 0 or 1 34% (31-38%) 55% (50-59%) 68% (63-73%) 81% (76-85%) 90% (85-94%) ECOG >=2 17% (11-24%) 42% (28-55%) 60% (40-75%) 72% (48-86%) 86% (55-96%) M0/M1a/M1b 33% (29-38%) 52% (46-58%) 67% (60-73%) 81% (73-86%) 90% (83-94%) M1c/M1d 29% (25-33%) 54% (47-60%) 67% (59-74%) 79% (71-85%) 90% (82-94%) Complete response 77% (71-82%) 82% (76-87%) 88% (82-92%) 91% (85-95%) 95% (90-98%) Partial response 27% (21-33%) 36% (28-43%) 50% (41-59%) 68% (57-78%) 88% (76-94%) PD1-inhibitor only 28% (24-32%) 47% (42-52%) 62% (56-68%) 77% (70-82%) 89% (83-93%) PD1 with CTLA4 38% (32-44%) 66% (57-73%) 78% (69-85%) 87% (77-93%) 92% (82-96%)