Efficacy of adjuvant therapy in patients with stage IIIA cutaneous melanoma
1Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Department of Medical Oncology, Fiona Stanley Hospital, Perth, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, Australia.
Background:
Patients with resected American Joint Committee on Cancer eighth edition (AJCC v8) stage IIIA melanoma have been underrepresented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted therapy and immunotherapy in this population is unclear.
Patients And Methods:
In this multicentre, retrospective study, patients with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab [anti-programmed cell death protein 1 (PD-1)], BRAF/MEK-targeted therapy dabrafenib + trametinib (TT) or no adjuvant treatment [observation (OBS)] were included. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and toxicity rates were examined.
Results:
A total of 628 patients from 34 centres across Australia, Europe and the United States were identified-256 in anti-PD-1, 80 in TT and 292 in OBS. The median follow-up was 2.6 years (interquartile range 1.6-3.4 years). The presence of some key poor prognostic variables was significantly higher in anti-PD-1 compared with OBS. The 2-year RFS was 79.3% [95% confidence interval (CI) 74.1% to 84.8%] for anti-PD-1, 98.6% (95% CI 96.0% to 100%) for TT and 84.3% (95% CI 79.9% to 89.0%) for OBS. The 2-year DMFS was 88.4% (95% CI 84.3% to 92.8%) in anti-PD-1, 100% in TT and 91.1% (95% CI 87.7% to 94.7%) in OBS. Higher Breslow thickness and higher mitotic rate were associated with higher risk of recurrence in anti-PD-1 and OBS (P < 0.05). Rates of ≥grade 3 toxicities were 10.9% with anti-PD-1 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 the anti-PD-1 group and 12.5% in the TT group.
Conclusions:
Stage IIIA melanoma has a modest risk of recurrence. Adjuvant anti-PD-1 did not significantly improve RFS or DMFS compared with OBS alone. Adjuvant TT appears promising over anti-PD-1 or OBS. Outcomes after adjuvant therapy in this population needs further study in larger datasets with longer follow-up or prospective randomised trials.
Insights
Adjuvant targeted therapy (TT) shows promise for stage IIIA melanoma patients, outperforming anti-programmed cell death protein 1 (PD-1) immunotherapy and observation alone. Further research is needed to confirm these findings in larger studies.
Area of Science:
- Oncology
- Dermatology
- Clinical Trials
Background:
- Stage IIIA melanoma patients are underrepresented in adjuvant therapy trials.
- The efficacy of adjuvant targeted therapy and immunotherapy in this group remains unclear.
Purpose of the Study:
- To evaluate the effectiveness of adjuvant anti-programmed cell death protein 1 (PD-1) therapy, dabrafenib + trametinib (TT), and observation (OBS) in resected stage IIIA melanoma.
- To compare recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and toxicity rates across treatment groups.
Main Methods:
- Retrospective analysis of 628 patients with stage IIIA melanoma (AJCC v8) from 34 centers.
- Patients received adjuvant anti-PD-1, TT, or OBS.
- Outcomes assessed included RFS, DMFS, and toxicity rates.
Main Results:
- The 2-year RFS was 79.3% for anti-PD-1, 98.6% for TT, and 84.3% for OBS.
- The 2-year DMFS was 88.4% for anti-PD-1, 100% for TT, and 91.1% for OBS.
- Higher Breslow thickness and mitotic rate correlated with increased recurrence risk.
Conclusions:
- Adjuvant anti-PD-1 therapy did not significantly improve RFS or DMFS compared to observation in stage IIIA melanoma.
- Adjuvant TT demonstrated promising outcomes, potentially superior to anti-PD-1 or OBS.
- Further investigation with larger datasets and prospective trials is warranted for stage IIIA melanoma adjuvant therapy.
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