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Health-related quality of life impact in a randomised phase III study of the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma

European Journal of Cancer, 7, 51, pages 833 - 840, Article in Press

Abstract

Aim

To present the impact of treatments on health-related quality of life (HRQoL) from the double-blind, randomised phase III COMBI-d study that investigated the combination of dabrafenib and trametinib versus dabrafenib monotherapy in patients withBRAFV600E/K-mutant metastatic melanoma. COMBI-d showed significantly prolonged progression-free survival for the combination.

Methods

HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, a generic cancer questionnaire (completed at baseline, during study treatment, at progression and post progression) assessing various dimensions (global health/QoL, functional status, and symptom impact). A mixed-model, repeated-measures analyses of covariance evaluated differences between arms.

Results

Questionnaire completion rates were >95% at baseline, >85% to week 40 and >70% at disease progression. Baseline scores across both arms were comparable for all dimensions. Global health dimension scores were significantly better at weeks 8, 16 and 24 for patients receiving the combination during treatment and at progression. The majority of functional dimension scores (physical, social, role, emotional and cognitive functioning) trended in favour of the combination. Pain scores were significantly improved and clinically meaningful (6–13 point difference) for patients receiving the combination for all follow-up assessments versus those receiving dabrafenib monotherapy. For other symptom dimensions (nausea and vomiting, diarrhoea, dyspnoea, and constipation), scores trended in favour of dabrafenib monotherapy.

Conclusion

This analysis demonstrates that the combination of dabrafenib and trametinib provides better preservation of HRQoL and pain improvements versus dabrafenib monotherapy while also delaying progression. (Clinicaltrials.gov registration number: NCT01584648).

Keywords: Melanoma, Protein kinase inhibitors, Molecular targeted therapy, Proto-oncogene proteins B-raf, Dabrafenib, Trametinib.

Footnotes

a Universitätsklinikum Essen, Hufelandstr. 55, Essen 45147, Germany

b GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States

c Moscow City Oncology Hospital #62, Moscow 143423, Russia

d Petrov Research Institute of Oncology, 68 Leningradskaya Street, Saint Petersburg 197758, Russia

e University of Athens, Aghiou Thoma 17, Athens 11527, Greece

f Fondazione IRCCS Istituto Nazionale Tumori, via Giacomo Venezian, 1, Milan, Italy

g Service de Dermatologie, Centre Hospitalo-Universitaire Sainte-Marguerite, 270 Boulevard de Sainte-Marguerite, Marseille 13009, France

h Dnepropetrovsk State Medical Academy, Dzerzhyns’koho Street 9, Dnepropetrovsk 49044, Ukraine

i Department of Dermatology, University Hospital Tuebingen, Liebermeisterstraße 25, Tuebingen 72076, Germany

j APHP Dermatology CIC Hôpital Saint Louis, University Paris Diderot, INSERM U976, Avenue Claude Vellefaux, Paris 75010, France

k Royal Marsden Hospital, Fulham Road, London SW3 6JJ, United Kingdom

l Melanoma and Esophageal Oncology Unit, Veneto Oncology Institute-IRCCS, via Gattamelata, 64, Padua 35128, Italy

m Sir Charles Gairdner Hospital, Hospital Avenue, Perth, WA 6009, Australia

n Hospital Clinic, Carrer Villarroel 170, Barcelona 08036, Spain

o Papa Giovanni XIII Hospital, Piazza OMS 1, Bergamo 24127, Italy

p Massachusetts General Hospital Cancer Center, 55 Fruit St, Boston 02114, MA, United States

q Mount Vernon Cancer Centre, Rickmansworth Road, Northwood HA6 2RN, United Kingdom

r David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles 90095, CA, United States

s Gustave Roussy and Paris 11 University, 114 Rue Edouard Vaillant, Villejuif-Paris-Sud 94805, France

t Melanoma Institute Australia & The University of Sydney, 40 Rocklands Road, Sydney 2060, Australia

lowast Corresponding author at: Department of Dermatology, Universitätsklinikum Essen, Hufelandstr. 55, Essen 45147 Germany. Tel.: +49 201 723 4342; fax: +49 (0) 201 723 59 35.

1 Affiliation of M. Casey and G. Aktan at the time of the study.