Format

Send to

Choose Destination
Eur J Cancer. 2020 Jan 2;126:33-44. doi: 10.1016/j.ejca.2019.11.016. [Epub ahead of print]

Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma.

Author information

1
Melanoma Unit, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy. Electronic address: paolo.ascierto@gmail.com.
2
Department of Dermatology, University Hospital Zürich Skin Cancer Center and University Zürich, Zürich, Switzerland.
3
Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece.
4
Cancer Center, Massachusetts General Hospital, Boston, MA, USA.
5
Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.
6
Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy.
7
Department of Dermatology, National Institute of Oncology, Budapest, Hungary.
8
Department of Dermatology, University Hospital Tuebingen, Tuebingen, Germany.
9
Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany.
10
Department of Dermato-oncology, University Hospital Prague and Charles University First Medical Faculty, Prague, Czech Republic.
11
Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany.
12
Department of Medical Oncology, Isala, Zwolle, Netherlands.
13
Department of Dermatology, University Medical Center Mainz, Mainz, Germany.
14
Pfizer Inc., Boulder, CO, USA.
15
Service of Dermatology, Department of Medicine and Paris-Sud University, Gustave Roussy, Villejuif, France.

Abstract

BACKGROUND:

BRAF/MEK inhibitor combinations are established treatments for BRAF V600-mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Here, we report an updated analysis of the COLUMBUS (COmbined LGX818 [encorafenib] Used with MEK162 [binimetinib] in BRAF mutant Unresectable Skin cancer) trial with long-term follow-up.

METHODS:

In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300). An updated analysis was conducted that included PFS, OS, objective response rate, safety and tolerability and analyses of results by prognostic subgroups.

RESULTS:

At data cutoff, there were 116, 113 and 138 deaths in the COMBO450, ENCO300 and VEM treatment arms, respectively. The median OS was 33.6 months (95% confidence interval [CI], 24.4-39.2) for COMBO450, 23.5 months (95% CI, 19.6-33.6) for ENCO300 and 16.9 months (95% CI, 14.0-24.5) for VEM. Compared with VEM, COMBO450 decreased the risk of death by 39% (hazard ratio [HR], 0.61; 95% CI, 0.48-0.79). The updated median PFS for COMBO450 was 14.9 months (95% CI, 11.0-20.2), ENCO300 was 9.6 months (95% CI, 7.4-14.8) and VEM was 7.3 months (95% CI, 5.6-7.9). PFS was longer for COMBO450 vs VEM (HR, 0.51; 95% CI, 0.39-0.67). Landmark OS and PFS results show consistent results for each year analysed. Subgroups all favoured COMBO450 vs VEM.

CONCLUSIONS:

Updated PFS and OS results for COMBO450 from the COLUMBUS trial demonstrate a long-term benefit in patients with advanced BRAF V600-mutated melanoma.

KEYWORDS:

BRAF V600–mutant melanoma; BRAF inhibitor; MEK inhibitor; Overall survival

PMID:
31901705
DOI:
10.1016/j.ejca.2019.11.016
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center