E310: Impact of FDA Approvals on the Use of Adjuvant Systemic Therapy for Node-Positive Melanoma

FDA approvals of immune checkpoint inhibitors as adjuvant therapy for resected stage III melanoma were granted 2015-2019 based on recurrence-free survival benefit; targeted therapy (TT) was approved in 2018. In parallel, a new CoC quality measure assesses initiation of adjuvant therapy within 6 months of operation for Stage IIIB-D melanoma. Our aim here was to assess the use and timing of adjuvant therapy for lymph node-positive (LN+) melanoma patients and associated factors.

Methods:

We identified LN+ melanoma patients having LN surgery from 2004-2020 National Cancer Database data, restaged per AJCC8 criteria. Adjuvant therapy administration was assessed. Trends over time were evaluated with Cochran Armitage trend tests. Multivariable logistic regression was used to assess associated factors. Kaplan Meier estimates were used to evaluate overall survival (OS).

Results: Of 52,193 LN+ melanoma patients, median age 58 (IQR 47-69) years, 61% were male, and 56% privately insured. 14,480 (36%) were clinically LN+. Among 50,946 whose initial treatment was surgery, 8,996 (22%) were pathologic stage IIIA, 8,809 (21%) IIIB, 21,238 (51%) IIIC and 2,258 (5%) IIID. Immunotherapy was administered to 16,888 patients (35%) and chemotherapy (including TT) to 2,983 (6%). Median time to systemic adjuvant therapy was 64 (43-95) days from operation and was initiated within 6 months of operation in 97%. Adjuvant immunotherapy use increased from 28% in 2004 to 63% in 2020 (p< 0.001), most steeply from 2016 (Figure) for all substages. This correlated with higher pT category (pT3 OR 2.86, pT4 OR 3.09, both p< 0.001), pN2/N3 (vs pN1) disease (OR 1.29, p< 0.001) and later year of diagnosis (OR 1.12, p< 0.001). Black race (OR 0.79, p=0.02), Medicare (OR 0.75), Medicaid (OR 0.80) and no insurance (OR 0.70), all p< 0.001, were associated with lower odds of treatment with adjuvant immunotherapy. 5-year OS was higher for stage III patients receiving adjuvant immunotherapy versus not (IIIA 90% vs 86%, IIIB 78% vs 71%, IIIC 64% vs 49%, and IIID 42% vs 25%, each p< 0.001).

Conclusions:

The administration of adjuvant immunotherapy for stage III melanoma patients increased significantly from 2016 mirroring FDA approvals and, when given, adjuvant therapy was initiated within 180 days for 97%. OS was higher for patients treated with adjuvant immunotherapy. These data suggest clinical care gaps in possible under-treatment of Stage IIIB-D, Black, publicly insured and uninsured patients, as well as over-treatment of Stage IIIA patients for which further study is warranted.