Highlights
- •Patients experienced long-term survival benefit with trametinib in the 5-year follow-up analysis of METRIC study.
- •No statistically significant difference in overall survival was seen between the treatment arms.
- •Trametinib could be considered as an alternative therapeutic option for patients.
- •The findings can be a basis for future indirect comparisons against ongoing long-term studies of dabrafenib + trametinib.
Abstract
Background
Primary findings from the METRIC (TMT212A2301) study demonstrated that trametinib
improved progression-free survival (PFS) and overall survival (OS) compared with chemotherapy
in patients with unresectable or metastatic cutaneous melanoma with a BRAF V600 E/K mutation. However, clinical data characterising the long-term use of these
therapies in combination with BRAF inhibitors or as monotherapies are limited.
Methods
In this open-label, phase 3 study, 322 patients with BRAF V600 E/K–mutant metastatic melanoma were randomised in a 2:1 ratio to receive trametinib
(2 mg orally, once daily; n = 214) or chemotherapy (dacarbazine [1000 mg/m2] or paclitaxel [175 mg/m2] intravenously, every 3 weeks; n = 108). Patients who progressed on chemotherapy
were allowed to cross over and receive trametinib. Five-year results of efficacy and
safety analyses are reported.
Results
The median PFS was 4.9 months in the trametinib arm versus 1.5 months in the chemotherapy
arm (hazard ratio, 0.54; 95% confidence interval, 0.41–0.73). Landmark OS rates for
trametinib versus chemotherapy arms at 1 year, 2 years and 5 years were 60.9% versus
49.6%, 32.0% versus 29.4% and 13.3% versus 17.0%, respectively. Most patients (n = 70
[65%]) from the chemotherapy arm crossed over to the trametinib arm early in their
treatment. No unexpected adverse events were reported.
Conclusions
This 5-year follow-up of patients with BRAF V600 E/K–mutant metastatic melanoma on a targeted therapy demonstrates that long-term
use of trametinib is possible with no new or unexpected adverse events. Some patients
experienced long-term survival benefit with trametinib monotherapy (METRIC ClinicalTrials.gov number, NCT01245062.).
Keywords
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Article info
Publication history
Published online: January 25, 2019
Accepted:
December 5,
2018
Received in revised form:
November 30,
2018
Received:
November 21,
2018
Footnotes
☆Presented in part at: European Society of Medical Oncology (ESMO) 2017, Madrid, Spain.
Identification
Copyright
© 2019 Elsevier Ltd. All rights reserved.
