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

Authors
 Lu Si  ;  Xiaoshi Zhang  ;  Sang Joon Shin  ;  Yun Fan  ;  Chia-Chi Lin  ;  Tae Min Kim  ;  Arunee Dechaphunkul  ;  Jedzada Maneechavakajorn  ;  Chi Sing Wong  ;  Palanichamy Ilankumaran  ;  Dung-Yang Lee  ;  Eduard Gasal  ;  Haifu Li  ;  Jun Guo 
Citation
 EUROPEAN JOURNAL OF CANCER, Vol.135 : 31-38, 2020-08 
Journal Title
EUROPEAN JOURNAL OF CANCER
ISSN
 0959-8049 
Issue Date
2020-08
MeSH
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols / administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols / adverse effects ; Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics ; Asia ; Biomarkers, Tumor / genetics* ; Female ; Humans ; Imidazoles / administration & dosage* ; Imidazoles / adverse effects ; Imidazoles / pharmacokinetics ; Male ; Melanoma / drug therapy* ; Melanoma / genetics ; Melanoma / mortality ; Melanoma / pathology ; Middle Aged ; Mutation* ; Oximes / administration & dosage* ; Oximes / adverse effects ; Oximes / pharmacokinetics ; Progression-Free Survival ; Protein Kinase Inhibitors / administration & dosage* ; Protein Kinase Inhibitors / adverse effects ; Protein Kinase Inhibitors / pharmacokinetics ; Proto-Oncogene Proteins B-raf / genetics* ; Pyridones / administration & dosage* ; Pyridones / adverse effects ; Pyridones / pharmacokinetics ; Pyrimidinones / administration & dosage* ; Pyrimidinones / adverse effects ; Pyrimidinones / pharmacokinetics ; Skin Neoplasms / drug therapy* ; Skin Neoplasms / genetics ; Skin Neoplasms / mortality ; Skin Neoplasms / pathology ; Time Factors
Keywords
BRAF ; Chinese ; Dabrafenib ; Melanoma ; Trametinib
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0959804920302495
DOI
10.1016/j.ejca.2020.04.044
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Lee, Yong Sang(이용상) ORCID logo https://orcid.org/0000-0002-8234-8718
Chang, Hang Seok(장항석) ORCID logo https://orcid.org/0000-0002-5162-103X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184956
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