Highlights
- •Dabrafenib-trametinib was efficacious in East Asians with advanced BRAF V600-mutant cutaneous melanoma.
- •Efficacy and safety of dabrafenib-trametinib in East Asians was similar to global studies.
- •No new safety findings were observed with dabrafenib-trametinib in East Asian patients.
- •Dabrafenib-trametinib could be a treatment option for East Asians with BRAF V600-mutant melanoma.
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
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Article info
Publication history
Published online: June 10, 2020
Accepted:
April 30,
2020
Received in revised form:
April 16,
2020
Received:
December 16,
2019
Identification
Copyright
© 2020 Elsevier Ltd. All rights reserved.
