E325: Overall Survival Comparing Neoadjuvant versus Adjuvant Alone Immunotherapy in Clinical Stage III Melanoma

Recent data have shown promising advantages (including improved event-free survival) to the addition of neoadjuvant immune checkpoint blockade compared to adjuvant immunotherapy (AIT) alone in patients with clinical stage III resectable melanoma. The impact of neoadjuvant immunotherapy (NIT) on survival in this clinical setting, however, remains unknown. We examined a large national cohort to identify factors associated with receipt of NIT and examine survival outcomes in patients with clinical stage III melanoma undergoing surgery.

Methods:

The National Cancer Database (NCDB) was used to identify patients with clinical stage III melanoma from 2016 to 2019 who received either NIT or AIT in addition to surgical resection. Univariable analysis and multivariable logistic regression was used to analyze predictors of neoadjuvant therapy. Overall survival (OS) was determined using the Kaplan-Meier method.

Results:

Overall, 2,205 patients were identified, with 2,045 (93%) receiving AIT and 160 (7%) receiving NIT. The median age was 62 years (interquartile range 51 – 71), 96% of patients were White, and 65% were male. Factors associated with NIT included higher clinical N-stage (N3 vs N1 OR 2.2, 95% confidence interval [CI] 1.4-3.4), and treatment at an academic center (OR 2.0, 95% CI 1.4-2.9). Chemotherapy was administered to 8% of NIT patients compared to 3% of AIT patients (OR 2.7, 95% CI 1.3-5.7). The median number of nodes examined was 15 for NIT patients vs. 9 in the AIT group (p=0.014), with median 3 vs. 2 positive nodes for NIT vs. AIT group (p=0.008). Notably, there was no significant difference in patient age, sex, race, Charlson-Deyo comorbidity index, or insurance status between the two groups. With a median follow-up of 32 months, there was no difference in OS between the two cohorts at 3 years, with OS of 75% (95% CI 72-77%) for the AIT group and 77% (95% CI 70-85%) for the NIT group (p=0.3), Figure 1.

Conclusions:

NIT has increasingly been used in the management of patients with clinical stage III melanoma. In the present study, although NIT and AIT patients had similar 3 year survival, NIT patients presented with more advanced clinical nodal disease. Further prospective long-term data comparing sequencing of immunotherapy are eagerly awaited to better delineate the potential benefits of NIT.