Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Update on Overall Survival in COLUMBUS: A Randomized Phase 3 Trial of Encorafenib (ENCO) Plus Binimetinib (BINI) vs Vemurafenib (VEM) or ENCO in Patients With BRAF V600–Mutant Melanoma (#321)

Andrew Haydon 1 , Gabriella Liszkay 2 , Helen J Gogas 3 , Mario Mandala 4 , Ana Arance 5 , Claus Garbe 6 , Dirk Schadendorf 7 , Reinhard Dummer 8 , Paolo A Ascierto 9 , Caroline Robert 10 , Michael D Pickard 11 , Victor Sandor 11 , Ashwin Gollerkeri 11 , Keith T Flaherty 12
  1. Alfred Hospital, Melbourne, VIC, Australia
  2. Department of Dermatology, National Institute of Oncology, Budapest,, Hungary
  3. Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece
  4. Department of Oncology and Haematology, Papa Giovan;ni XXIII Cancer Center Hospital, Bergamo, Italy
  5. Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain
  6. Department of Dermatology, University Hospital Tuebingen, Tuebingen, Germany
  7. Department of Dermatology, University Hospital Essen, Essen, Germany
  8. Department of Dermatology, University Hospital Zürich Skin Cancer Center, Zürich, Switzerland
  9. Melanoma Unit, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy
  10. Service of Dermatology , Department of Medicine and Paris-Sud University, Gustave Roussy, France
  11. Array BioPharma, Boulder, CO, USA
  12. Cancer Center, Massachusetts General Hospital, Boston, MA, USA

BRAF/MEK-inhibitor combinations have a central role in the treatment of BRAF V600–mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Because of these meaningful improvements in outcome, mature landmark analyses of PFS and OS require long-term follow-up. Here we report an updated analysis of OS and other endpoints from the COLUMBUS trial.

In Part 1 of COLUMBUS, 577 patients with advanced/metastatic BRAF V600‒mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to ENCO 450 mg QD + BINI 45 mg BID (COMBO450) vs VEM 960 mg BID (VEM) or ENCO 300 mg QD (ENCO300). An updated analysis including PFS, OS, objective response rate (ORR), safety and tolerability, and analyses of results by prognostic subgroups including elevated lactate dehydrogenase (LDH) and degree of organ involvement was conducted after an additional 12 months’ follow-up.

At data cutoff, there were 116, 113, and 138 deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. Median follow-up for OS was 48.8 months (mo), with median OS of 33.6 mo (95% CI, 24.4–39.2) for COMBO450, 23.5 mo (95% CI, 19.6–33.6) for ENCO300, and 16.9 mo (95% CI, 14.0–24.5) for VEM. Compared to VEM, COMBO450 decreased the risk of death by 39% (HR, 0.61 [95% CI, 0.48–0.79). Updated median PFS by blinded central review was COMBO450, 14.9 mo (95% CI, 11.0–20.2), ENCO300, 9.6 mo (95% CI, 7.4–14.8), and VEM, 7.3 mo (95% CI, 5.6–7.9). PFS was longer for COMBO450 vs VEM (HR, 0.51 [95% CI, 0.39–0.67). Landmark OS and PFS results, as well as subgroup analyses and updated safety and tolerability, will be presented.

Updated PFS and OS results for COMBO450 from the COLUMBUS trial continue to represent new benchmarks for combined BRAF/MEK-inhibitor combinations for treatment of BRAF V600‒mutated melanoma.