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Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma.
- Source :
-
European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2019 Mar; Vol. 109, pp. 61-69. Date of Electronic Publication: 2019 Jan 25. - Publication Year :
- 2019
-
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.<br />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/m <superscript>2</superscript> ] or paclitaxel [175 mg/m <superscript>2</superscript> ] 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.<br />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.<br />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.).<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Brain Neoplasms genetics
Brain Neoplasms secondary
Dacarbazine administration & dosage
Female
Follow-Up Studies
Humans
Male
Melanoma genetics
Melanoma pathology
Melanoma secondary
Middle Aged
Paclitaxel administration & dosage
Prognosis
Pyridones administration & dosage
Pyrimidinones administration & dosage
Skin Neoplasms genetics
Skin Neoplasms pathology
Skin Neoplasms secondary
Survival Rate
Time Factors
Young Adult
Melanoma, Cutaneous Malignant
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Brain Neoplasms drug therapy
Melanoma drug therapy
Mutation
Proto-Oncogene Proteins B-raf genetics
Skin Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0852
- Volume :
- 109
- Database :
- MEDLINE
- Journal :
- European journal of cancer (Oxford, England : 1990)
- Publication Type :
- Academic Journal
- Accession number :
- 30690294
- Full Text :
- https://doi.org/10.1016/j.ejca.2018.12.015