Patients with resected American Joint Committee on Cancer 8 ^th edition (AJCC v8) stage IIIA melanoma have been under-represented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear.
In this multicenter, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab (anti-PD1), BRAF/MEK-targeted therapy dabrafenib + trametinib (TT), or no adjuvant treatment (OBS) were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and toxicity rates were examined.
A total of 628 patients from 34 centers across Australia, Europe and USA were identified - 256 in anti-PD1, 80 in TT and 292 in OBS. The median follow-up was 2.6 years (IQR, 1.6-3.4 years). The presence of some key poor prognostic variables was significantly higher in anti-PD1 compared to OBS. The two-year RFS was 79.3% (95% CI, 74.1-84.8) for anti-PD1, 98.6% (95% CI, 96.0-100) for TT and 84.3% (95% CI, 79.9-89.0) for OBS. The two-year DMFS was 88.4% (95% CI, 84.3-92.8) in anti-PD1, 100% in TT and 91.1% (95% CI, 87.7-94.7) in OBS. Higher Breslow thickness and higher mitotic rate were associated with higher risk of recurrence in the anti-PD1 and OBS (P<0.05). Rates of ≥ Grade 3 toxicities were 10.9% with anti-PD1 and 17.5% with TT; discontinuation due to toxicity occurred in 13.3% and 21.2%, respectively. Rates of unresolved toxicity at last follow-up were 26.9% in anti-PD1 and 12.5% in TT groups.
Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD1 did not significantly improve RFS or DMFS compared to OBS alone. Adjuvant TT appears promising over anti-PD1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow up or prospective randomised trials.