Overall survival outcomes in stage III melanoma patients treated with adjuvant immunotherapy vs targeted therapy: A National Cancer Database analysis.

9575 Background: Adjuvant therapy with immunotherapy (IO) and targeted therapy (TT) has significantly improved outcomes in Stage III melanoma following surgical resection. While both approaches demonstrate efficacy, head-to-head comparisons remain limited, and real-world evidence on overall survival (OS) across diverse subgroups is sparse. This study compares OS between adjuvant IO and TT using data from the National Cancer Database (NCDB) from 2018 to 2020, offering insights into subgroup-specific benefits. Methods: We conducted a retrospective cohort study of Stage III melanoma patients from the NCDB diagnosed between 2018 and 2019 who underwent definitive surgical resection followed by either IO or TT. Patients receiving neoadjuvant therapy were excluded. OS was analyzed using Kaplan-Meier survival curves and compared using log-rank tests. Hazard ratios (HR) with 95% confidence intervals (CI) were derived from Cox proportional hazards models, adjusted for demographic and clinical covariates. Subgroup analysis was performed to identify populations deriving differential benefit from IO. Results: A total of 1,493 patients met the inclusion criteria (IO: 1,352; TT: 141). Overall survival (OS) was significantly higher in the IO group (74.9%; 95% CI: 72.2–77.8% at 3 years) compared to the TT group (62.1%; 95% CI: 52.5–73.3% at 3 years) (p = 0.0055). Subgroup analysis revealed that the survival benefit with IO was more pronounced in patients aged <65 years (HR 0.49; 95% CI: 0.32–0.75), males (HR 0.54; 95% CI: 0.37–0.77), those with private insurance (HR 0.45; 95% CI: 0.27–0.76), and primary tumors located on the head and neck (HR 0.44; 95% CI: 0.22–0.89). No subgroup demonstrated superior outcomes with TT. Conclusions: In this NCDB-based analysis, adjuvant IO was associated with a significant OS advantage compared to TT in Stage III melanoma patients. However, NCDB limitations, including lack of information on specific agents (e.g., BRAF/MEK inhibitors or checkpoint inhibitors), must be acknowledged. Additionally, this analysis reflects OS rather than melanoma-specific survival (MSS). In the NCDB sample, there was a 10:1 preference for IO over TT, reflecting marked community preference for IO. These findings appear to indicate that IO is the preferred adjuvant strategy, though further prospective studies are required to validate subgroup-specific outcomes and confirm these results.