Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376724" target="_blank" >RIV/00216208:11110/18:10376724 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/18:10376724

Result on the web

<a href="https://doi.org/10.1016/S1470-2045(18)30142-6" target="_blank" >https://doi.org/10.1016/S1470-2045(18)30142-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S1470-2045(18)30142-6" target="_blank" >10.1016/S1470-2045(18)30142-6</a>

Result language

angličtina

Original language name

Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial

Original language description

Background: Combined BRAF-MEK inhibitor therapy is the standard of care for BRAF(V600)-mutant advanced melanoma. We investigated encorafenib, a BRAF inhibitor with unique target-binding properties, alone or in combination with the MEK inhibitor binimetinib, versus vemurafenib in patients with advanced BRAFV600-mutant melanoma. Methods: COLUMBUS was conducted as a two-part, randomised, open-label phase 3 study at 162 hospitals in 28 countries. Eligible patients were aged 18 years or older and had histologically confirmed locally advanced (American Joint Committee on Cancer [AJCC] stage IIIB, IIIC, or IV), unresectable or metastatic cutaneous melanoma, or unknown primary melanoma; a BRAF(V600E) or BRAF(V600K) mutation; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; and were treatment naive or had progressed on or after previous first-line immunotherapy. In part 1 of the study, patients were randomly assigned (1:1:1) via interactive response technology to receive either oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily (encorafenib plus binimetinib group), oral encorafenib 300 mg once daily (encorafenib group), or oral vemurafenib 960 mg twice daily (vemurafenib group). The primary endpoint was progression-free survival by blinded independent central review for encorafenib plus binimetinib versus vemurafenib. Efficacy analyses were by intention-to-treat. Safety was analysed in patients who received at least one dose of study drug and one postbaseline safety assessment. The results of part 2 will be published separately. This study is registered with ClinicalTrials.gov, number NCT01909453, and EudraCT, number 2013-001176-38. Findings: Between Dec 30, 2013, and April 10, 2015, 577 of 1345 screened patients were randomly assigned to either the encorafenib plus binimetinib group (n=192), the encorafenib group (n=194), or the vemurafenib group (n=191). With a median follow-up of 16.6 months (95% CI 14.8-16.9), median progression-free survival was 14.9 months (95% CI 11.0-18.5) in the encorafenib plus binimetinib group and 7.3 months (5.6-8.2) in the vemurafenib group (hazard ratio [HR] 0.54, 95% CI 0.41-0.71; two-sided p&lt;0.0001). The most common grade 3-4 adverse events seen in more than 5% of patients in the encorafenib plus binimetinib group were increased gamma-glutamyltransferase (18 [9%] of 192 patients), increased creatine phosphokinase (13 [7%]), and hypertension (11 [6%]); in the encorafenib group they were palmoplantar erythrodysaesthesia syndrome (26 [14%] of 192 patients), myalgia (19 [10%]), and arthralgia (18 [9%]); and in the vemurafenib group it was arthralgia (11 [6%] of 186 patients). There were no treatment-related deaths except for one death in the combination group, which was considered possibly related to treatment by the investigator. Interpretation: Encorafenib plus binimetinib and encorafenib monotherapy showed favourable efficacy compared with vemurafenib. Overall, encorafenib plus binimetinib appears to have an improved tolerability profile compared with encorafenib or vemurafenib. Encorafenib plus binimetinib could represent a new treatment option for patients with BRAF-mutant melanoma.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30216 - Dermatology and venereal diseases

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

The Lancet: Oncology

ISSN

1470-2045

e-ISSN

—

Volume of the periodical

19

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

603-615

UT code for WoS article

000431003000042

EID of the result in the Scopus database

2-s2.0-85044302834