title: 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.
abstract: OBJECTIVE
  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 with BRAF V600E/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.
  
  
  CONCLUSIONS
  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).
authors: Universitätsklinikum Essen, Hufelandstr. 55, Essen 45147, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de.
authors: Dirk
authors: D
authors: Schadendorf
authors: GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: mayur.m.amonkar@gsk.com.
authors: Mayur M
authors: MM
authors: Amonkar
authors: Moscow City Oncology Hospital #62, Moscow 143423, Russia. Electronic address: sdaniel@mail.ru.
authors: Daniil
authors: D
authors: Stroyakovskiy
authors: Petrov Research Institute of Oncology, 68 Leningradskaya Street, Saint Petersburg 197758, Russia. Electronic address: levchenko@newmail.ru.
authors: Evgeny
authors: E
authors: Levchenko
authors: University of Athens, Aghiou Thoma 17, Athens 11527, Greece. Electronic address: hgogas@hol.gr.
authors: Helen
authors: H
authors: Gogas
authors: Fondazione IRCCS Istituto Nazionale Tumori, via Giacomo Venezian, 1, Milan, Italy. Electronic address: filippo.debraud@istitutotumori.mi.it.
authors: Filippo
authors: F
authors: de Braud
authors: Service de Dermatologie, Centre Hospitalo-Universitaire Sainte-Marguerite, 270 Boulevard de Sainte-Marguerite, Marseille 13009, France. Electronic address: jean-jacques.grob@ap-hm.fr.
authors: Jean-Jacques
authors: JJ
authors: Grob
authors: Dnepropetrovsk State Medical Academy, Dzerzhyns'koho Street 9, Dnepropetrovsk 49044, Ukraine. Electronic address: oncology@dsma.dp.ua.
authors: Igor
authors: I
authors: Bondarenko
authors: Department of Dermatology, University Hospital Tuebingen, Liebermeisterstraße 25, Tuebingen 72076, Germany. Electronic address: claus.garbe@med.uni-tuebingen.de.
authors: Claus
authors: C
authors: Garbe
authors: APHP Dermatology CIC Hôpital Saint Louis, University Paris Diderot, INSERM U976, Avenue Claude Vellefaux, Paris 75010, France. Electronic address: celeste.lebbe@sls.aphp.fr.
authors: Celeste
authors: C
authors: Lebbe
authors: Royal Marsden Hospital, Fulham Road, London SW3 6JJ, United Kingdom. Electronic address: james.larkin@rmh.nhs.uk.
authors: James
authors: J
authors: Larkin
authors: Melanoma and Esophageal Oncology Unit, Veneto Oncology Institute-IRCCS, via Gattamelata, 64, Padua 35128, Italy. Electronic address: mgaliz@tiscali.it.
authors: Vanna
authors: V
authors: Chiarion-Sileni
authors: Sir Charles Gairdner Hospital, Hospital Avenue, Perth, WA 6009, Australia. Electronic address: michael.millward@uwa.edu.au.
authors: Michael
authors: M
authors: Millward
authors: Hospital Clinic, Carrer Villarroel 170, Barcelona 08036, Spain. Electronic address: amarance@clinic.ub.es.
authors: Ana
authors: A
authors: Arance
authors: Papa Giovanni XIII Hospital, Piazza OMS 1, Bergamo 24127, Italy. Electronic address: mmandala@hpg23.it.
authors: Mario
authors: M
authors: Mandalà
authors: Massachusetts General Hospital Cancer Center, 55 Fruit St, Boston 02114, MA, United States. Electronic address: kflaherty@partners.org.
authors: Keith T
authors: KT
authors: Flaherty
authors: Mount Vernon Cancer Centre, Rickmansworth Road, Northwood HA6 2RN, United Kingdom. Electronic address: p.nathan@nhs.net.
authors: Paul
authors: P
authors: Nathan
authors: David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles 90095, CA, United States. Electronic address: aribas@mednet.ucla.edu.
authors: Antoni
authors: A
authors: Ribas
authors: Gustave Roussy and Paris 11 University, 114 Rue Edouard Vaillant, Villejuif-Paris-Sud 94805, France. Electronic address: Caroline.Robert@igr.fr.
authors: Caroline
authors: C
authors: Robert
authors: GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: meshellcasey@yahoo.com.
authors: Michelle
authors: M
authors: Casey
authors: GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: douglas.j.demarini@gsk.com.
authors: Douglas J
authors: DJ
authors: DeMarini
authors: GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: jhangir.g.irani@gsk.com.
authors: Jhangir G
authors: JG
authors: Irani
authors: GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: gursel.aktan@gmail.com.
authors: Gursel
authors: G
authors: Aktan
authors: Melanoma Institute Australia & The University of Sydney, 40 Rocklands Road, Sydney 2060, Australia. Electronic address: georgina.long@sydney.edu.au.
authors: Georgina V
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authors: Long
mesh_terms: D019943:Amino Acid Substitution; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006304:Health Status; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis; D010091:Oximes / Q000008:administration & dosage* / Q000009:adverse effects; D010147:Pain Measurement; D000090063:Proto-Oncogene Mas; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014633:Valine / Q000235:genetics
chemical_list: D007093:Imidazoles; C000715470:MAS1 protein, human; D010091:Oximes; D000090063:Proto-Oncogene Mas; D011728:Pyridones; D011744:Pyrimidinones; C560077:trametinib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D014633:Valine; C561627:dabrafenib
keywords: Dabrafenib; Melanoma; Molecular targeted therapy; Protein kinase inhibitors; Proto-oncogene proteins B-raf; Trametinib