Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma.

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.).

• Authors: Caroline Robert, Keith Flaherty, Paul Nathan, Peter Hersey, Claus Garbe, Mohammed Milhem, Lev Demidov, Peter Mohr, Jessica C Hassel, Piotr Rutkowski, Reinhard Dummer, Jochen Utikal, Felix Kiecker, James Larkin, Anthony D'Amelio Jr, Bijoyesh Mookerjee, Dirk Schadendorf
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 109 Pg. 61-69 (03 2019) ISSN: 1879-0852 [Electronic] England
• PMID: 30690294 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Pyridones
• Pyrimidinones
• trametinib
• Dacarbazine
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Brain Neoplasms (drug therapy, genetics, secondary)
• Dacarbazine (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Male
• Melanoma (drug therapy, genetics, pathology, secondary)
• Middle Aged
• Mutation
• Paclitaxel (administration & dosage)
• Prognosis
• Proto-Oncogene Proteins B-raf (genetics)
• Pyridones (administration & dosage)
• Pyrimidinones (administration & dosage)
• Skin Neoplasms (drug therapy, genetics, pathology, secondary)
• Survival Rate
• Time Factors
• Young Adult