Abstract 1098P
Background
Approximately 5% of patients with macroscopic regional metastatic melanoma presents with unresectable locally advanced disease. This makes treatment according to standard of care in stage III melanoma, consisting of complete surgical resection and adjuvant systemic therapy, unfeasible.
Methods
In this prospective, single center, single arm phase II trial, 25 patients with BRAF-mutated unresectable stage III melanoma were planned to be included and treated with BRAF and MEK inhibitors dabrafenib (D) 150 mg BID and trametinib (T) 2 mg QD for 8 weeks. If sufficient downsizing occurred, evaluated on PET/CT (week 2 and 8) and by physical examination, patients would proceed to surgery. The primary endpoint was the percentage of patients achieving an R0 resection (tumor free margins) and treatment was considered effective if this was accomplished in at least 8 patients.
Results
Accrual was terminated after inclusion of 21 patients due to achievement of predefined endpoints, slow inclusion rate and changing treatment landscape. All 21 patients completed D+T treatment, of which 2 developed progressive disease after 2 and 8 weeks. The remaining 19 patients proceeded to surgery, of which 17 (81%) achieved an R0 resection. One patient had an R1 resection and in 1 patient no resection was performed due to encasement of vital structures. Pathologic responses were assessed in 18 patients undergoing a resection: 8 (44%) patients had a pathologic complete response (pCR), 8 (44%) a pathologic partial response (pPR) and 2 (11%) showed no pathologic response. At a median follow-up of 43.3 months (IQR 25.9-48.9 months), a median RFS of 9.9 months was seen in patients undergoing surgery. The median OS was not reached. The treatment was well tolerated, with 71% grade 1-2 adverse events (AE), 19% grade 3 AEs. The most commonly reported toxicity was fever (48%).
Conclusions
Neoadjuvant dabrafenib and trametinib shows to be a potent cytoreductive treatment, enabling a radical resection in 17/21 (81%) patients with prior unresectable regionally advanced melanoma.
Clinical trial identification
NL45261.031.13.
Editorial acknowledgement
Legal entity responsible for the study
NKI-AVL.
Funding
Novartis.
Disclosure
A.C.J. van Akkooi: Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: MSD-Merck; Advisory/Consultancy: Merck-Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: 4SC. J.B.A.G. Haanen: Advisory/Consultancy, Shareholder/Stockholder/Stock options: Neogene Therapeutics; Advisory/Consultancy: Aimm; Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Celsius; Advisory/Consultancy: Gadeta; Advisory/Consultancy, Research grant/Funding (institution): GSK; Advisory/Consultancy: Immunocore; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Neon; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Achilles; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Vaximm. All other authors have declared no conflicts of interest.