Dirk Schadendorf1, Mayur M Amonkar2, Daniil Stroyakovskiy3, Evgeny Levchenko4, Helen Gogas5, Filippo de Braud6, Jean-Jacques Grob7, Igor Bondarenko8, Claus Garbe9, Celeste Lebbe10, James Larkin11, Vanna Chiarion-Sileni12, Michael Millward13, Ana Arance14, Mario Mandalà15, Keith T Flaherty16, Paul Nathan17, Antoni Ribas18, Caroline Robert19, Michelle Casey20, Douglas J DeMarini21, Jhangir G Irani22, Gursel Aktan23, Georgina V Long24. 1. Universitätsklinikum Essen, Hufelandstr. 55, Essen 45147, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de. 2. GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: mayur.m.amonkar@gsk.com. 3. Moscow City Oncology Hospital #62, Moscow 143423, Russia. Electronic address: sdaniel@mail.ru. 4. Petrov Research Institute of Oncology, 68 Leningradskaya Street, Saint Petersburg 197758, Russia. Electronic address: levchenko@newmail.ru. 5. University of Athens, Aghiou Thoma 17, Athens 11527, Greece. Electronic address: hgogas@hol.gr. 6. Fondazione IRCCS Istituto Nazionale Tumori, via Giacomo Venezian, 1, Milan, Italy. Electronic address: filippo.debraud@istitutotumori.mi.it. 7. Service de Dermatologie, Centre Hospitalo-Universitaire Sainte-Marguerite, 270 Boulevard de Sainte-Marguerite, Marseille 13009, France. Electronic address: jean-jacques.grob@ap-hm.fr. 8. Dnepropetrovsk State Medical Academy, Dzerzhyns'koho Street 9, Dnepropetrovsk 49044, Ukraine. Electronic address: oncology@dsma.dp.ua. 9. Department of Dermatology, University Hospital Tuebingen, Liebermeisterstraße 25, Tuebingen 72076, Germany. Electronic address: claus.garbe@med.uni-tuebingen.de. 10. APHP Dermatology CIC Hôpital Saint Louis, University Paris Diderot, INSERM U976, Avenue Claude Vellefaux, Paris 75010, France. Electronic address: celeste.lebbe@sls.aphp.fr. 11. Royal Marsden Hospital, Fulham Road, London SW3 6JJ, United Kingdom. Electronic address: james.larkin@rmh.nhs.uk. 12. Melanoma and Esophageal Oncology Unit, Veneto Oncology Institute-IRCCS, via Gattamelata, 64, Padua 35128, Italy. Electronic address: mgaliz@tiscali.it. 13. Sir Charles Gairdner Hospital, Hospital Avenue, Perth, WA 6009, Australia. Electronic address: michael.millward@uwa.edu.au. 14. Hospital Clinic, Carrer Villarroel 170, Barcelona 08036, Spain. Electronic address: amarance@clinic.ub.es. 15. Papa Giovanni XIII Hospital, Piazza OMS 1, Bergamo 24127, Italy. Electronic address: mmandala@hpg23.it. 16. Massachusetts General Hospital Cancer Center, 55 Fruit St, Boston 02114, MA, United States. Electronic address: kflaherty@partners.org. 17. Mount Vernon Cancer Centre, Rickmansworth Road, Northwood HA6 2RN, United Kingdom. Electronic address: p.nathan@nhs.net. 18. David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles 90095, CA, United States. Electronic address: aribas@mednet.ucla.edu. 19. Gustave Roussy and Paris 11 University, 114 Rue Edouard Vaillant, Villejuif-Paris-Sud 94805, France. Electronic address: Caroline.Robert@igr.fr. 20. GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: meshellcasey@yahoo.com. 21. GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: douglas.j.demarini@gsk.com. 22. GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: jhangir.g.irani@gsk.com. 23. GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA 19426, United States. Electronic address: gursel.aktan@gmail.com. 24. Melanoma Institute Australia & The University of Sydney, 40 Rocklands Road, Sydney 2060, Australia. Electronic address: georgina.long@sydney.edu.au.
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 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. 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).
RCT Entities:
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 with BRAFV600E/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).
Authors: Drew C Deniger; Mei Li M Kwong; Anna Pasetto; Mark E Dudley; John R Wunderlich; Michelle M Langhan; Chyi-Chia Richard Lee; Steven A Rosenberg Journal: Clin Cancer Res Date: 2016-10-07 Impact factor: 12.531
Authors: Thomas M Atkinson; Angela M Stover; Daniel F Storfer; Rebecca M Saracino; Thomas A D'Agostino; Denise Pergolizzi; Konstantina Matsoukas; Yuelin Li; Ethan Basch Journal: Epidemiol Rev Date: 2017-01-01 Impact factor: 6.222
Authors: Paolo A Ascierto; Michael Atkins; Carlo Bifulco; Gerardo Botti; Alistair Cochran; Michael Davies; Sandra Demaria; Reinhard Dummer; Soldano Ferrone; Silvia Formenti; Thomas F Gajewski; Claus Garbe; Samir Khleif; Rolf Kiessling; Roger Lo; Paul Lorigan; Grant Mc Arthur; Giuseppe Masucci; Ignacio Melero; Martin Mihm; Giuseppe Palmieri; Giorgio Parmiani; Igor Puzanov; Pedro Romero; Bastian Schilling; Barbara Seliger; David Stroncek; Janis Taube; Sara Tomei; Hassane M Zarour; Alessandro Testori; Ena Wang; Jérôme Galon; Gennaro Ciliberto; Nicola Mozzillo; Francesco M Marincola; Magdalena Thurin Journal: J Transl Med Date: 2015-11-30 Impact factor: 5.531