Five-year analysis of neoadjuvant dabrafenib and trametinib for stage III melanoma
May 30, 2024
Abstract
Background
Neoadjuvant dabrafenib plus trametinib has a high pathological response rate and impressive short-term survival in patients with resectable stage III melanoma. We report five-year outcomes from the phase II NeoCombi trial.
Methods
NeoCombi (NCT01972347) was a single-arm, open-label, single-centre, phase II trial. Eligible patients were adults (aged ≥18) with histologically-confirmed, resectable, RECIST-measurable AJCC 7th ed. clinical stage IIIB–C BRAF V600E/K-mutant melanoma and Eastern Co-operative Oncology Group performance status ≤1. Patients received 52 weeks of treatment with 150 mg dabrafenib (orally twice per day) plus 2 mg trametinib (orally once per day), with complete resection of the pre-therapy tumour bed at Week 12.
Results
Between August 20, 2014, and April 19, 2017, 35 patients were enrolled. At data cut-off (August 17, 2021), the median follow-up was 60 months (95% CI 56–72). Overall, 21 of 35 (60%) patients recurred, including twelve (57%) with first recurrence in locoregional sites (followed by later distant recurrence in six) and nine (43%) with first recurrence in distant sites, including three in the brain. Most recurrences occurred within two years, with no recurrences beyond three years. At five years, recurrence-free survival was 40% (95% CI 27–60), distant metastasis-free survival was 57% [95% CI 42–76%], and overall survival was 80% (95% CI 67–94). Five-year survival outcomes were stratified by pathological response: recurrence-free survival was 53% with pCR versus 28% with non-pCR (p=0.087), distant metastasis-free survival was 59% versus 55% (p=0.647), and overall survival was 88% versus 71% (p=0.205), respectively.
Conclusions
Neoadjuvant dabrafenib plus trametinib has high pathological response rates in clinical stage III melanoma, but low rates of recurrence-free survival, similar to those achieved with adjuvant targeted therapy alone. Patients with a pCR to dabrafenib plus trametinib still had a high risk of recurrence, unlike that seen with immunotherapy where recurrences are rare.
Source:
Alexander M. Menzies, Serigne N. Lo, Robyn P.M. Saw, Maria Gonzalez, Sydney Ch’ng, Omgo E. Nieweg, Kerwin F. Shannon, Peter M. Ferguson, Jenny Lee, Louise Emmett, Rony Kapoor, Robert V. Rawson, Jonathan R. Stretch, John F. Thompson, Andrew J. Spillane, Helen Rizos, Richard A. Scolyer, Georgina V. Long, Five-year analysis of neoadjuvant dabrafenib and trametinib for stage III melanoma, Annals of Oncology, 2024, , ISSN 0923-7534, https://doi.org/10.1016/j.annonc.2024.05.002.