Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS).


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
07 2021
Historique:
received: 01 04 2021
accepted: 20 04 2021
pubmed: 7 6 2021
medline: 11 11 2021
entrez: 6 6 2021
Statut: ppublish

Résumé

In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment. Here, results on health-related quality of life (HRQoL) are presented. COLUMBUS was a two-part, open-label, randomised, phase III study in patients with BRAF-mutant melanoma. In PART-I, 577 patients were randomised (1:1:1) to encorafenib plus binimetinib, encorafenib or vemurafenib. The primary objective was to assess progression-free survival. As a secondary objective, HRQoL was assessed by the EQ-5D, the EORTC QLQ-C30 and the FACT-M questionnaires. Furthermore, time to definitive 10% deterioration was estimated with a Kaplan-Meier analysis and differences in mean scores between groups were calculated with a mixed-effect model for repeated measures. Hospitalisation rate and the impact of hospitalisation on HRQoL were also assessed. Patients receiving the combination treatment showed improvement of their FACT-M and EORTC QLQ-C30 global health status scores, compared to those receiving vemurafenib (post-baseline score differences: 3.03 [p < 0.0001] for FACT M and 5.28 [p = 0.0042] for EORTC QLQ-C30), indicative of a meaningful change in patient's status. Furthermore, a delay in the deterioration of QoL was observed in non-hospitalised patients compared to hospitalised patients (hazard ratio [95% CI]: 1.16 [0.80; 1.68] for EORTC QLQ-C30 and 1.27 [0.81; 1.99] for FACT-M) and a risk reduction of 10% deterioration, favoured the combination in both groups. The improved efficacy of encorafenib plus binimetinib compared to vemurafenib, translates into a positive impact on the perceived health status as assessed by the HRQoL questionnaires. The study is registered with ClinicalTrials.gov, number NCT01909453 and EudraCT number 2013-001176-38.

Sections du résumé

BACKGROUND
In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment. Here, results on health-related quality of life (HRQoL) are presented.
METHODS
COLUMBUS was a two-part, open-label, randomised, phase III study in patients with BRAF-mutant melanoma. In PART-I, 577 patients were randomised (1:1:1) to encorafenib plus binimetinib, encorafenib or vemurafenib. The primary objective was to assess progression-free survival. As a secondary objective, HRQoL was assessed by the EQ-5D, the EORTC QLQ-C30 and the FACT-M questionnaires. Furthermore, time to definitive 10% deterioration was estimated with a Kaplan-Meier analysis and differences in mean scores between groups were calculated with a mixed-effect model for repeated measures. Hospitalisation rate and the impact of hospitalisation on HRQoL were also assessed.
RESULTS
Patients receiving the combination treatment showed improvement of their FACT-M and EORTC QLQ-C30 global health status scores, compared to those receiving vemurafenib (post-baseline score differences: 3.03 [p < 0.0001] for FACT M and 5.28 [p = 0.0042] for EORTC QLQ-C30), indicative of a meaningful change in patient's status. Furthermore, a delay in the deterioration of QoL was observed in non-hospitalised patients compared to hospitalised patients (hazard ratio [95% CI]: 1.16 [0.80; 1.68] for EORTC QLQ-C30 and 1.27 [0.81; 1.99] for FACT-M) and a risk reduction of 10% deterioration, favoured the combination in both groups.
CONCLUSION
The improved efficacy of encorafenib plus binimetinib compared to vemurafenib, translates into a positive impact on the perceived health status as assessed by the HRQoL questionnaires. The study is registered with ClinicalTrials.gov, number NCT01909453 and EudraCT number 2013-001176-38.

Identifiants

pubmed: 34091420
pii: S0959-8049(21)00274-4
doi: 10.1016/j.ejca.2021.04.028
pii:
doi:

Substances chimiques

Benzimidazoles 0
Carbamates 0
Sulfonamides 0
binimetinib 181R97MR71
Vemurafenib 207SMY3FQT
encorafenib 8L7891MRB6
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1

Banques de données

ClinicalTrials.gov
['NCT01909453']
EudraCT
['2013-001176-38']

Types de publication

Clinical Trial, Phase III Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

116-128

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2021 Elsevier Ltd. All rights reserved.

Auteurs

Helen Gogas (H)

National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece. Electronic address: helgogas@gmail.com.

Reinhard Dummer (R)

University Hospital Zürich Skin Cancer Center, Zürich, Switzerland.

Paolo A Ascierto (PA)

Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy.

Ana Arance (A)

Hospital Clinic of Barcelona, Barcelona, Spain.

Mario Mandalà (M)

Unit of Medical Oncology, University of Perugia, Perugia, Italy.

Gabriella Liszkay (G)

National Institute of Oncology, Budapest, Hungary.

Claus Garbe (C)

Eberhard Karls University, Tuebingen, Germany.

Dirk Schadendorf (D)

University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany.

Ivana Krajsová (I)

University Hospital Prague and Charles University First Medical Faculty, Prague, Czech Republic.

Ralf Gutzmer (R)

Hannover Medical School, Hannover, Germany.

Vanna Chiarion Sileni (VC)

Oncology Institute of Veneto IRCCS, Padua, Italy.

Caroline Dutriaux (C)

University Hospital Centre Bordeaux, Hôpital Saint-André, Bordeaux, France.

Naoya Yamazaki (N)

Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Carmen Loquai (C)

University Medical Center, Mainz, Germany.

Paola Queirolo (P)

Division of Medical Oncology for Melanoma, Sarcoma, and Rare Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Groot Jan de Willem (G)

Department of Medical Oncology, Isala Oncological Center, Zwolle, Netherlands.

Abir Tadmouri Sellier (AT)

Pierre Fabre Medicament, Boulogne-Billancourt, France.

Jeanne Suissa (J)

Pierre Fabre Medicament, Boulogne-Billancourt, France.

Juliette Murris (J)

Pierre Fabre Medicament, Boulogne-Billancourt, France.

Ashwin Gollerkeri (A)

At Time of Research: Pfizer Inc., Boulder, CO, USA.

Caroline Robert (C)

Institute Gustave Roussy, Villejuif, France.

Keith T Flaherty (KT)

Massachusetts General Hospital, Boston, MA, USA.

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Classifications MeSH