- 12 months of adjuvant dabrafenib (D) plus trametinib (T) confers a long-term survival benefit in patients with resected stage III BRAF V600E/K-mutant melanoma.
Why this matters
- This analysis represents the longest follow-up to date from a phase 3 study of a standard-of-care adjuvant therapy for patients with resected stage III BRAF-mutant melanoma.
- The phase 3 COMBI-AD trial enrolled 870 patients with completely resected V600E/K-mutant melanoma.
- Patients were randomly assigned (1:1; stratification by BRAF status and disease substage) to 12 months of D+T or to placebo.
- Primary endpoint: relapse-free survival (RFS).
- Secondary endpoints included OS and distant metastasis-free survival (DMFS).
- Funding: Novartis Pharmaceuticals Corporation.
- Minimum study follow-up was 60 months for the D+T group and 59 months for the placebo group.
- 190/438 patients in the D+T group and 262/432 patients in the placebo group experienced an RFS event.
- Median RFS was not reached (NR) in the D+T group and was 16.6 months with placebo (HR, 0.51; 95% CI, 0.42-0.61).
- 5-year RFS rates:
- 52% (95% CI, 48%-58%) with D+T.
- 36% (95% CI, 32%-41%) with placebo.
- RFS curves for both groups appear to be plateauing.
- The RFS benefit with D+T was evident across all American Joint Committee on Cancer (AJCC) 7 substages and across AJCC 8 substages IIIB, IIIC, and IIID.
- Median DMFS was NR in either arm but favored D+T (HR, 0.55; 95% CI, 0.44-0.70).
- OS was not updated because the prespecified number of events had not yet occurred.
- Safety data were not updated because all patients had completed study treatment by the time of primary analysis.
- The absence of RFS benefit for substage AJCC 8 IIIA may relate to the low number of events.