Journal article
Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K–mutant advanced or metastatic melanoma
European journal of cancer (1990), Vol.109, pp.61-69
03/2019
DOI: 10.1016/j.ejca.2018.12.015
PMID: 30690294
Abstract
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.
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.
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.
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.).
•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.
Details
- Title: Subtitle
- Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K–mutant advanced or metastatic melanoma
- Creators
- Caroline Robert - Institut Gustave RoussyKeith Flaherty - Massachusetts General HospitalPaul Nathan - Mount Vernon Cancer CentrePeter Hersey - The University of SydneyClaus Garbe - University of TübingenMohammed Milhem - University of IowaLev Demidov - Ministry of HealthPeter Mohr - Elbe Kliniken Stade-BuxtehudeJessica C. Hassel - University Hospital HeidelbergPiotr Rutkowski - The Maria Sklodowska-Curie National Research Institute of OncologyReinhard Dummer - University Hospital of ZurichJochen Utikal - German Cancer Research CenterFelix Kiecker - Charité - Universitätsmedizin BerlinJames Larkin - Royal Marsden HospitalAnthony D'Amelio - Novartis Pharmaceuticals Corporation East Hanover NJ USA.Bijoyesh Mookerjee - Novartis Pharmaceuticals Corporation East Hanover NJ USA.Dirk Schadendorf - Essen University Hospital
- Resource Type
- Journal article
- Publication Details
- European journal of cancer (1990), Vol.109, pp.61-69
- DOI
- 10.1016/j.ejca.2018.12.015
- PMID
- 30690294
- NLM abbreviation
- Eur J Cancer
- ISSN
- 0959-8049
- eISSN
- 1879-0852
- Publisher
- Elsevier Ltd
- Grant note
- DOI: 10.13039/100004330, name: GlaxoSmithKline; DOI: 10.13039/501100020274, name: EUSA Pharma
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359565602771
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