Survival Outcomes of Patients with Clinical Stage III Melanoma in the Era of Novel Systemic Therapies

Background. Immune checkpoint and BRAF-targeted inhibitors have demonstrated significant survival benefits for advanced melanoma patients within the context of clinical trials. We sought to determine their impact on overall survival (OS) at a population level in order to better understand the current landscape for patients diagnosed with clinical stage III melanoma. Methods. A retrospective study was performed using the National Cancer Database. Patients diagnosed with clinical stage III melanoma were categorized by diagnosis year into two cohorts preceding the advent of novel therapies (P1: 2004-2005, P2: 2008-2009) and a contemporary group (P3: 2012-2013). OS was estimated using standard time-to-event statistical methods. Results. Of 3720 patients, 525 (14%) were diagnosed in P1, 1375 (37%) in P2, and 1820 (49%) in P3. Median age at diagnosis increased over time (58, 59, and 61 years in P1, P2, and P3, respectively, P = 0.004). OS increased between P2 (median 49.3 months) and P3 (median 58.2 months, Bonferroni-corrected log-rank P < 0.001) but did not differ between P1 (median 50.5 months) and P2 (Bonferroni-corrected log-rank P > 0.99). These differences persisted on multivariable analysis. OS improved for patients diagnosed in P3 compared with P1 [hazard ratio (HR) 0.76, P < 0.001] but not P2 compared with P1 (HR 0.96, P = 0.52). Conclusions. OS has significantly improved nationally for patients newly diagnosed with clinical stage III melanoma in the era of novel melanoma therapies. OS outcomes will likely continue to evolve as these agents are increasingly utilized in the adjuvant setting. These data may help to better inform affected patients with respect to prognosis.