1245P - Quality-of-Life (QoL) in COLUMBUS Part 1: A Phase 3 Trial of Encorafenib (ENCO) Plus Binimetinib (BINI) Versus Vemurafenib (VEM) or ENCO in BRAF-Mu...

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Cancer in Adolescents
Melanoma and other Skin Tumours
Personalised Medicine
Presenter Helen Gogas
Citation Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377
Authors H. Gogas1, R. Dummer2, P.A. Ascierto3, A.M. Arance4, M. Mandala5, G. Liszkay6, C. Garbe7, D. Schadendorf8, I. Krajsová9, R. Gutzmer10, V. Chiarion Sileni11, C. Dutriaux12, J.W.B. de Groot13, N. Yamazaki14, C. Loquai15, L.A. de Parseval16, M. Pickard17, V. Sandor18, C. Robert19, K.T. Flaherty20
  • 1Internal Medicine, National and Kapodistrian University of Athens, Laikon Hospital, 11527 - Athens/GR
  • 2Department Of Dermatology, Universitätsspital Zürich - Skin Cancer Center University Hospital, Zürich/CH
  • 3Unit Of Melanoma, Cancer Immunotherapy And Innovative Therapy, Istituto Nazionale Tumori Fondazione Pascale, Naples/IT
  • 4Department Of Medical Oncology, Hospital Clinic of Barcelona, Barcelona/ES
  • 5Department Of Oncology And Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo/IT
  • 6Department Of Dermatology, National Institute of Oncology, Budapest/HU
  • 7Department Of Dermatology, Division Of Dermatooncology, Eberhard Karls University, Tuebingen/DE
  • 8Department Of Dermatology, University Hospital Essen, Essen/DE
  • 9Department Of Dermato-oncology, University Hospital Prague and Charles University First Medical Faculty, Prague/CZ
  • 10Department Of Dermatology And Allergy, Skin Cancer Center, Hannover Medical School, Hannover/DE
  • 11Melanoma Cancer Unit, Oncology Institute of Veneto IRCCS, Padua/IT
  • 12Department Of Oncologic Dermatology, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux/FR
  • 13Department Of Medical Oncology, Isala, Zwolle/NL
  • 14Department Of Dermatologic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 15Department Of Dermatology, University Medical Center, Mainz/DE
  • 16Translational Clinical Oncology, Novartis Pharma AG, Basel/CH
  • 17Biostatistics And Data Management, Array BioPharma Inc., Boulder/US
  • 18Medical Affairs, Array BioPharma, Boulder/US
  • 19Department Of Medicine, Institute Gustave Roussy, Villejuif/FR
  • 20Department Of Medical Oncology, Massachusetts General Hospital, Boston/US

Abstract

Background

In COLUMBUS Part 1, the BRAF inhibitor ENCO 450 mg once daily (QD) + the mitogen-activated protein kinase kinase (MEK) inhibitor BINI 45 mg twice daily (BID; COMBO450) improved progression-free survival vs VEM 960 mg BID alone and ENCO 300 mg QD (ENCO300) alone in patients (pts) with advanced BRAF V600-mutant melanoma. Tolerability of COMBO450 was favorable compared with VEM or ENCO300. Here we compare patient-reported health-related QoL between the treatment arms.

Methods

Pts were randomized 1:1:1 to receive COMBO450, VEM, or ENCO300. Patient-reported health-related QoL was assessed by 2 validated instruments, the Functional Assessment of Cancer Therapy–Melanoma (FACT-M) questionnaire and the European Organization for Research and Treatment of Cancer’s Quality of Life Questionnaire–Core 30 (EORTC QLQ-C30). Higher scores represent better QoL on both instruments. A mixed-effect model for repeated measures was used to compare the change from baseline (BL) in the domain scores over time.

Results

Among 577 pts, 192 were randomized to COMBO450, 191 were randomized to VEM, and 194 were randomized ENCO300. Compliance of pts completing the FACT-M and EORTC QLQ-C30 questionnaires was equivalent; approximately 80%–90% of pts still at risk completed the assessment from BL through cycle 25. Mean BL FACT-M scores were similar between arms (52.39, 52.01, and 52.84 in the COMBO450, VEM, and ENCO300 arms, respectively). FACT-M subscale change over time indicated that COMB450 was associated with an estimated 2.98 point higher post-BL score vs VEM (95% confidence interval [CI] 1.34–4.63) and a 4.01 pt higher post-BL score vs ENCO300 (95% CI 2.47–5.54). Mean EORTC QLQ-C30 scores at BL were 66.72, 64.74, and 66.10 with COMBO450, VEM, and ENCO300, respectively. Evaluation of change over time found that COMBO450 was associated with an estimated 5.25 point higher post-BL score vs VEM (95% CI 1.21–9.29) and an 8.32 higher post-BL score vs ENCO300 (95% CI 4.54–12.11).

Conclusions

Patient-reported health-related QoL was rated consistently and significantly better with COMBO450 vs VEM or ENCO monotherapy.

Clinical trial identification

Trial protocol number, CMEK162B2301 (release date, July 13, 2015)

Legal entity responsible for the study

Array BioPharma Inc

Funding

Array BioPharma Inc and Novartis Pharmaceuticals Corporation

Disclosure

H. Gogas: Consultant for Roche, Bristol-Myers Squibb, MSD, Novartis, and Amgen. R. Dummer: Honoraria from and consulting/advisory role for Roche, Bristol-Myers Squib, GSK, MSD, Novartis, and Amgen; research funding from Roche, Bristol-Myers Squibb, GSK, MSD, and Novartis. P.A. Ascierto: Consulting fees from Bristol-Myers Squibb, Roche/Genentech, MSD, Ventana, Novartis, Amgen, and Array BioPharma; research funding from Bristol-Myers Squibb, Roche/Genentech, Ventana, and Array BioPharma A. Arance: Honoraria from and consulting/advisory role and speakers bureau for Novartis, Roche, MSD, and Bristol-Myers Squib; travel expenses from Roche and Bristol-Myers Squibb. M. Mandala: Honoraria from Novartis, GSK, Bristol-Myers Squibb, MSD, and Roche; speakers bureau for Novartis, GSK, Roche, and Bristol-Myers Squib; advisory board member for Novartis, Amgen, MSD, and Bristol-Myers Squib; research funding from Roche. C. Garbe: Honoraria and travel expenses from and served in a consulting/advisory role and speakers bureau member for Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche, and Philogen; has received research funding for University Hospital Tübingen from Bristol-Myers Squibb, Novartis, and Roche. D. Schadendorf: Honoraria and travel expenses from and consulting/advisory role and speakers bureau for Amgen, Bristol-Myers Squib, Novartis, Roche, and MSD; research funding for University Hospital Essen from Amgen, Bristol-Myers Squibb, Novartis, Roche, and MSD. I. Krajsová: Advisory board member for Bristol-Myers Squibb, Novartis, Roche, MSD; travel expenses from Bristol-Myers Squibb and MSD. R. Gutzmer: Consulting fees and/or honoraria from Roche, Bristol-Myers Squibb, MSD, GSK, Novartis, Almirall, LEO, Amgen, Pfizer, Pierre Fabre Merck Serono, Boehringer Ingelheim; research funding from Roche, Novartis, Pfizer, Johnson & Johnson; travel expenses from Bristol-Myers Squibb, Roche. V. Chiarion Sileni: Honoraria received from Novartis, GSK, Bristol-Myers Squibb, MSD, and Roche; speakers bureau for Novartis, GSK, Roche, and Bristol-Myers Squibb; advisory board member for Novartis, Amgen, MSD, Bristol-Myers Squibb, and Roche. J.W.B. de Groot: Consulting/advisory role for Amgen, Bayer, Celgene, Roche, Bristol-Myers Squibb, GSK, MSD, and Merck Serono. N. Yamazaki: Advisory role for Chugai Pharma, Bristol-Myers Squibb Japan, and Ono Pharmaceutical; honoraria from Chugai Pharma, Bristol-Myers Squibb Japan, Ono Pharmaceutical, GlaxoSmithKline, Takeda, AstraZeneca Japan, Boehringer Ingelheim, and Maruho. C. Loquai: Advisory board member for Roche, Novartis, Bristol-Myers Squibb, MSD, Biontech, Amgen, and Pierre Fabre; speakers fees from Roche, Novartis, Bristol-Myers Squib, and MSD; travel expenses from Roche, Novartis, Bristol-Myers Squibb, MSD, and Amgen. L.A. de Parseval: Employee of Novartis Pharma AG; may own stock or stock options. M. Pickard: Employee of Array BioPharma; may own stock or stock options. V. Sandor: Employee/leadership role at Array BioPharma; stock or other ownership of Array BioPharma and Incyte Corp. C. Robert: Consultant for Roche, Novartis, Bristol-Myers Squibb, MSD, and Amgen. K.T. Flaherty: Honoraria from and consulting/advisory role for Novartis and Array BioPharma; research funding from Novartis. All other authors have declared no conflicts of interest.