Dabrafenib plus trametinib boasts high pathological response for stage III melanoma

Pathological response rates are high for neoadjuvant dabrafenib plus trametinib among patients with stage III melanoma, but recurrence-free survival (RFS) rates are low, reports a study.

This single-arm, open-label, single-centre, phase II trial included 35 adult patients with histologically confirmed, resectable, RECIST-measurable, American Joint Committee on Cancer seventh edition clinical stage IIIB-C BRAF V600E/K-mutant melanoma and Eastern Cooperative Oncology Group performance status ≤1. Participants were enrolled between 20 August 2014 and 19 April 2017.

Patients were treated with dabrafenib 150 mg (orally twice per day) plus trametinib 2 mg (orally once per day) for 52 weeks, with complete resection of the pretherapy tumour bed at week 12. The median follow-up was 60 months.

Twenty-one patients (60 percent) had a recurrence, including 12 (57 percent) with first recurrence in locoregional sites (followed by later distant recurrence in six) and nine (43 percent) in distant sites, with three occurring in the brain. Most of these recurrences happened within 2 years, and none occurred beyond 3 years.

Five-year RFS was 40 percent (95 percent CI, 27‒60), distant metastasis-free survival (DMFS) was 57 percent (95 percent CI, 42‒76), and overall survival (OS) was 80 percent (95 percent CI, 67‒94).

Survival outcomes at 5 years were stratified by pathological response: RFS, 53 percent with pCR vs 28 percent with non-pCR (p=0.087); DMFS, 59 percent vs 55 percent (p=0.647); and OS, 88 percent vs 71 percent (p=0.205).

“Patients with a pCR to dabrafenib plus trametinib still had a high risk of recurrence, unlike that seen with immunotherapy where recurrences are rare,” the investigators said.