5-year overall survival after adjuvant treatment for stage III melanoma: An English nationwide registry-based study.

Abstract

9570 Background: Adjuvant treatments for stage III cutaneous melanoma were approved based on significant improvement in recurrence free survival (RFS) with both anti-PD-1 and BRAF+MEK inhibitors. However, registration trials have not demonstrated a significant overall survival (OS) benefit to date. Given the potential patient and financial toxicity associated with adjuvant therapy, the effect on OS remains an important consideration. Methods: A retrospective study linking national registry data for all patients diagnosed with stage III melanoma in England between 2016 and 2021 were included and divided into two cohorts based on date of initial melanoma diagnostic staging: pre- and post-May 2018, when adjuvant therapy was initially approved in England. Key data collected were: patient age, sex, date of stage III melanoma diagnosis, TNM stage, systemic therapy for melanoma, cause and date of death. Data cut-off for follow-up was 1 st August 2025. Melanoma-specific survival (MSS) and OS were calculated using the Kaplan-Meier method and Cox regression analyses. Results: A total of 6,297 patients were analysed (pre-May 2018: n=2,089; post-May 2018: n=4,208). Survival outcomes improved significantly in the post-adjuvant cohort. The 5-year overall survival (OS) rose from 60.9% (95% CI: 58.8–63.0) to 64.2% (95% CI: 62.7–65.7), with a hazard ratio of 0.89 (95% CI: 0.82–0.96; p=0.004). Similarly, 5-year melanoma-specific survival (MSS) improved from 70.4% (95% CI: 68.4–72.5) to 72.8% (95% CI: 71.4–74.3), HR 0.89 (95% CI: 0.81–0.99; p=0.025). When stratifying by age, sex or melanoma TNM stage, no significant OS or MSS was observed. Conclusions: English national registry data demonstrates a statistically significant improvement in both OS and MSS for patients diagnosed with stage III melanoma after approval of adjuvant therapy for stage III melanoma. This is consistent with published real world data from France, but contrasts with findings in Sweden and the Netherlands. The reduced utilisation of subsequent therapy for metastatic disease likely reflects the established RFS benefit. The OS benefits are modest, so careful discussion of the potential risks and benefits of adjuvant therapy remains central to patient care. Cohort Pre-May 2018 Post-May 2018 Hazard ratio(95% CI) Number (N) 2,089 4,208 Median duration of follow up (years) 8.38 6.23 Median age (range) 66 (18,103) 67 (18,102) Stage (AJCC V8)3A3B3C3D3 (unspecified) 127 (6.1%)161 (7.7%)1042 (49.9%)97 (4.6%)662 (31.7%) 487 (11.6%)698 (16.6%)2085 (49.5%)168 (4%)770 (18.3%) Received adjuvant systemic therapy 148*(7%) 1772(42%) Received systemic therapy for metastatic melanoma 676(32%) 685(16%) 5-year OS (95% CI) 60.9 %(58.8 – 63.0) 64.2%(62.7 – 65.7) 0.89(0.82 – 0.96) p = 0.004 5-year MSS (95% CI) 70.4%(68.4 - 72.5) 72.8%(71.4 - 74.3) 0.89(0.81 – 0.99)p = 0.025