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

• Verfasst von: Robert, Caroline [VerfasserIn]
• Verfasst von: Hassel, Jessica C. [VerfasserIn]
• Verfasst von: Utikal, Jochen [VerfasserIn]
• Titel: Five-year outcomes from a phase 3 METRIC study in patients with BRAF V600 E/K-mutant advanced or metastatic melanoma*
• Verf.angabe: 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, Bijoyesh Mookerjee, Dirk Schadendorf
• E-Jahr: 2019
• Jahr: 25 January 2019
• Umfang: 9 S.
• Fussnoten: Gesehen am 10.09.2019
• Titel Quelle: Enthalten in: European journal of cancer
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1992
• Jahr Quelle: 2019
• Band/Heft Quelle: 109(2019), Seite 61-69
• ISSN Quelle: 1879-0852
• DOI: doi:10.1016/j.ejca.2018.12.015
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: inhibitor
• Sach-SW: METRIC
• Sach-SW: Survival
• Sach-SW: Targeted therapy
• Sach-SW: Trametinib
• K10plus-PPN: 1675737525

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.).