1244P - Hospitalization Rates 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 Ana Arance
Citation Annals of Oncology (2017) 28 (suppl_5): v428-v448. 10.1093/annonc/mdx377
Authors A. Arance1, R. Dummer2, P.A. Ascierto3, H. Gogas4, 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
  • 1Department Of Medical Oncology, Hospital Clínic Barcelona, 08036 - Barcelon/ES
  • 2Department Of Dermatology, UniversitätsSpital Zürich, Skin Cancer Center University Hospital, 8091 - Zürich/CH
  • 3Unit Of Melanoma, Cancer Immunotherapy And Innovative Therapy, Istituto Nazionale Tumori Fondazione Pascale, Naples/IT
  • 4Department Of Internal Medicine, National and Kapodestrian University of Athens, Laikon Hospital, Athens/GR
  • 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
  • 13Medical 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

Part 1 of the COLUMBUS study demonstrated that the BRAF inhibitor ENCO 450 mg once daily (QD) + the 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 evaluate resource utilization based on hospitalization data (ClinicalTrials.gov, NCT01909453; EudraCT, 2013-001176-38).

Methods

Pts were randomized 1:1:1 to receive COMBO450, VEM, or ENCO300. Efficacy endpoints, including the number of pts hospitalized and number of hospitalizations, were described. Time to first occurrence of hospitalization was assessed by the Kaplan-Meier method. Hospitalization endpoints were adjusted per 100 pt-months (pt-mo) of exposure to study drug.

Results

Among 577 pts, 192 were randomized to COMBO450, 191 were randomized to VEM, and 194 were randomized ENCO300. Exposure-adjusted hospitalization rates (per 100 pt-mo) were 3.5% in the COMBO450 arm compared with 4.3% and 6.2% in the ENCO300 and VEM arms, respectively. Exposure-adjusted mean duration of hospitalization per 100 pt-mo was 32.5, 38.2, and 53.7 days in the COMBO450, ENCO300, and VEM arms, respectively. Median (95% CI) time to first hospitalization for pts with ≥1 event was 5.1 (2.6–6.1) mo in the COMBO450 arm compared with 2.8 (0.8–4.2) and 2.8 (2.0–3.8) mo in the ENCO300 and VEM arms, respectively.

Conclusions

Resource utilization, as determined by hospitalization data in COLUMBUS Part 1, was lower with COMBO450 compared with VEM or ENCO300 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

A. Arance: Honoraria from and consulting/advisory role and speakers bureaus for Novartis, Roche, MSD, and Bristol-Myers Squibb; travel expenses from Roche and Bristol-Myers Squibb. R. Dummer: Honoraria from and consulting/advisory role for Roche, Bristol-Myers Squibb, 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 H. Gogas: Consultant for Roche, Bristol-Myers Squibb, MSD, Novartis, and Amgen. M. Mandala: Honoraria from Novartis, GSK, Bristol-Myers Squibb, MSD, and Roche; speakers bureaus for Novartis, GSK, Roche, and Bristol-Myers Squibb; advisory board member for Novartis, Amgen, MSD, and Bristol-Myers Squibb; research funding from Roche. C. Garbe: Honoraria and travel expenses from and served in a consulting/advisory role and as speakers bureau member for Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche, and Philogen; has received research funding for University Hospital Tuebingen from Bristol-Myers Squibb, Novartis, and Roche. D. Schadendorf: Honoraria and travel expenses from and consulting/advisory role and speakers bureaus for Amgen, Bristol-Myers Squibb, 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 bureaus 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, Pierre Fabre, and Amgen; speakers fees from Roche, Novartis, Bristol-Myers Squibb, 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.