Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (29573941)
Authors Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Chiarion-Sileni V, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Moutouh-de Parseval LA, Pickard MD, Sandor V, Robert C, Flaherty KT
Title Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.
Journal The Lancet. Oncology
Vol 19
Issue 5
Date 2018 May
URL
Abstract Text Combined BRAF-MEK inhibitor therapy is the standard of care for BRAFV600-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.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 BRAFV600E or BRAFV600K 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.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<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 γ-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.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.Array BioPharma, Novartis.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600K melanoma sensitive Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453) and both BRAF V600E and BRAF V600K are on the companion diagnostic. 29573941 detail... detail... detail...
BRAF V600E melanoma sensitive Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453), and both BRAF V600E and V600K are on the companion diagnostic. 29573941 detail... detail... detail...
BRAF V600E/K melanoma sensitive Binimetinib + Encorafenib FDA approved - On Companion Diagnostic Actionable In a Phase III (COLUMBUS) trial that supported FDA approval, Braftovi (encorafenib) in combination with Mektovi (binimetinib) demonstrated improved tolerability profile and efficacy, resulted in a progression-free survival of 14.9 months in patients with advanced melanoma harboring BRAF V600E/K mutations, comparing to 7.3 months in the Zelboraf (vemurafenib) group (HR=0.54, p<0.0001) (PMID: 29573941; NCT01909453) and both BRAF V600E and V600K are on the companion diagnostic. 29573941 detail... detail... detail...