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Clinical Trial
. 2020 Aug:135:31-38.
doi: 10.1016/j.ejca.2020.04.044. Epub 2020 Jun 10.

Open-label, phase IIa study of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma

Lu Si  1 , Xiaoshi Zhang  2 , Sang Joon Shin  3 , Yun Fan  4 , Chia-Chi Lin  5 , Tae Min Kim  6 , Arunee Dechaphunkul  7 , Jedzada Maneechavakajorn  8 , Chi Sing Wong  9 , Palanichamy Ilankumaran  10 , Dung-Yang Lee  10 , Eduard Gasal  10 , Haifu Li  11 , Jun Guo  12
Affiliations
Clinical Trial

Open-label, phase IIa study of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma

Lu Si et al. Eur J Cancer. 2020 Aug.

Abstract

Purpose: This study (NCT02083354) assessed the efficacy and safety of dabrafenib plus trametinib in East Asian patients with advanced BRAF V600-mutant cutaneous melanoma.

Method: Overall, 77 patients of East Asian origin (including 61 from Mainland China) with unresectable or metastatic BRAF V600-mutant cutaneous melanoma were enrolled. Prior treatment was allowed except with BRAF/MEK inhibitors. Patients received dabrafenib 150 mg twice daily and trametinib 2 mg once daily. The primary end-point was objective response rate (ORR) using Response Evaluation Criteria in Solid Tumours 1.1. Secondary end-points were duration of response (DOR), progression-free survival (PFS), overall survival (OS), pharmacokinetics and safety.

Results: At data cutoff (February 23, 2018; median follow-up, 8.3 months), treatment was ongoing in 36 patients (47%). The median age was 52 years; 32% of patients had elevated lactate dehydrogenase, and 84% had received prior systemic therapy. ORR was 61% (95% confidence interval: 49.2-72.0), with four patients (5%) achieving complete response. Median DOR and PFS were 11.3 and 7.9 months, respectively. Median OS was not reached. The most common adverse event (AE) of any grade was pyrexia (56%). Grade ≥III AEs occurred in 29 patients (38%). The most common grade ≥III AEs were pyrexia (8%) and anaemia (6%). AEs led to permanent discontinuation in five patients (6.5%). Mean Cmax for dabrafenib and trametinib was 3560 and 11.5 ng/mL (day 1) and 2680 and 27.1 ng/mL (day 15), respectively.

Conclusion: These results support the efficacy and tolerability of dabrafenib in combination with trametinib in East Asian patients with unresectable or metastatic BRAF V600-mutant cutaneous melanoma.

Keywords: BRAF; Chinese; Dabrafenib; Melanoma; Trametinib.

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Conflict of interest statement

Conflict of interest statement L.S. has received speakers’ honoraria from MSD, Roche, Novartis, Shanghai Junshi Biosciences and OrienGene. T.M.K. reports receiving grants from AZ-KHIDI outside of the submitted work. C.S.W. reports receiving grants from Novartis during the conduct of the study. P.I., E.G. and H.L. are employees of Novartis. D-Y.L. is a former employee of Novartis. J.G. has consulting/advisory roles in Bayer, MSD, Novartis, OrienGene, Roche, Shanghai Junshi Biosciences and Simcere Pharmaceutical Group. No potential conflicts of interest were disclosed by the other authors.

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