5042 - An open-label, non-randomized, phase IIIb study of trametinib in combination with dabrafenib for patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma

Background

Regimens combining BRAF and MEK inhibitors have revolutionized the treatment of patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant cutaneous melanoma. As only dabrafenib (D) was available in France, the objective of this study was to provide access to T and to assess, in the French population, the benefits of the combination of T (D+T) previously reported.

Methods

This single arm, open label, multicenter, non-randomized study included patients with histologically confirmed stage III unresectable or IV BRAF V600-mutant melanoma, with or without brain metastases (BM). Patients received D (150 mg twice/day) combined with T (2 mg once/day). Outcomes were overall response rate (ORR), progression-free survival (PFS), and frequencies of adverse events (AEs). Median PFS was estimated using the Kaplan-Meier method.

Results

Between March 2015 and November 2016, 914 patients were screened in 40 French centers and 856 received at least one dose of D+T. The table presents baseline characteristics. Median followup was 5.63 months. ORR was 50.2% in the overall population and 41.5% in patients with BM. Median PFS was 8.02 months (95% CI, [7.33-8.77]) in the overall population and 5.68 months (95% CI, [5.29-6.87]) in patients with BM. The safety profile was consistent with previous reports. Among AEs of special interest, pyrexia/hyperthermia was the most frequent: 38.2% (327/856) all grades; grade (G) 1 29.0%, G2 14.8%, G3 4.0% and G4 0.5%.Table: 1260P

Baseline demographic and disease characteristics

Abbreviations: ECOG= Eastern Cooperative Oncology Group; PS= Performance Status; LDH= Lactate Dehydrogenase; SD= Standard Deviation. Footnotes: ^a Data was missing for 2 patients ^b Percentage based on subjects with M1c stage at screening (N = 617) ^c Based on patients with known LDH at baseline (N = 628)

Conclusions

This is, to date, the largest prospective study worldwide in BRAF V600-mutant cutaneous melanoma patients treated with the D+T combination. It confirms the efficacy and tolerability of D+T in this population, including pts with BM.

Clinical trial identification

NCT02416232.

Legal entity responsible for the study

Novartis Pharma S.A.S. (France) Novartis Pharma S.A.S. (France).

Funding

Novartis Pharma S.A.S. (France).

Editorial Acknowledgement

Editorial assistance in the writting of the abstract was provided by Jone Iriondo-Alberdi (PhD) of ITEC Services.

Disclosure

P. Saiag: Advisory board: BMS, MSD, Novartis, GSK, Merck Serono, Roche, Novartis, Pierre Fabre, Amgen. C. Robert: Honoraria, Consulting, Advisory board: Amgen, BMS, Merck, Novartis, Roche, GSK. J.J. Grob: Honoraria: BMS, MSD, Roche, Novartis, Amgen, Merck, Pierre Fabre, Pfizer, Incyte; Consulting or advisory role: BMS, MSD, Roche, Novartis, Amgen, Merck, Pierre Fabre, Pfizer, Incyte; Research funding (self and institution), Travel, accomodation, expenses: BMS, Roche, MSD. L. Mortier: Honoraria: BMS, MSD, Roche, Novartis, Amgen, Merck, Incyte; Consulting or advisory role: BMS, MSD, Roche, Novartis, Amgen, Merck, Incyte; Travel, accomodations, expenses: BMS, Roche, MSD. C. Lebbe: Honoraria: BMS, MSD, Roche, Novartis, Amgen, Merck, Pierre Fabre, Pfizer, Incyte; Consulting or advisory role: BMS; Research funding (self and institution), Travel, accommodation, expenses: BMS, MSD. S. Mansard: Advisory board, Travel expenses: Novartis, BMS, MSD, Roche. E-M. Neidhardt: Advisory board: Novartis, BMS. T. Lesimple: Advisory board: Roche, Novartis, MSD, Incyte. C. Bedane: Advisory board: Novartis; Investigator: Combi I study. A. Szenik, A. Denden: Employee: Novartis. C. Dutriaux: Advisory boards, Investigator: Roche, Amgen, BMS, MSD, Merk Serono, Novartis. All other authors have declared no conflicts of interest.