e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Five-year overall survival (OS) in COLUMBUS: A randomized phase 3 trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients (pts) with BRAF V600-mutant melanoma. (#230)

Andrew Haydon 1 , Reinhard Dummer 2 , Keith Flaherty 3 , Caroline Robert 4 , Ana M Arance 5 , Jan Willem de Groot 6 , Clause Garbe 7 , Helen Gogas 8 , Ralf Gutzmer 9 , Ivana Krajsová 10 , Gabriella Liszkay 11 , Carmen Loquai 12 , Mario Mandalà 13 , Dirk Schadendorf 14 , Naoya Yamazaki 15 , Fabien Zohren 16 , Victoria Atkinson 17 , Michael Millward 18 , Andrew Hill 19 20 , Michelle L Edwards 21 , Paolo A Ascierto 22
  1. Medical Oncology Department, The Alfred, Melbourne, Victoria, Australia
  2. University Hospital Zurich, Zurich, Switzerland
  3. Massachusetts General Hospital, Boston, Massachusetts, United States of America
  4. Institut Gustave Roussy, Villejuif, France
  5. Hospital Clinic of Barcelona, Barcelona, Spain
  6. Isala Oncology Center, Zwolle, Netherlands
  7. University Hospital Tübingen, Tübingen, Germany
  8. National and Kapodistrian University of Athens, Athens, Greece
  9. Hannover Medical School, Hannover, Germany
  10. University Hospital Prague , Prague, Czech Republic
  11. National Institute of Oncology, Budapest, Hungary
  12. University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
  13. University of Perugia, Perugia, Italy
  14. West German Cancer Center, Essen, Germany
  15. National Cancer Center Hospital, Tokyo, Japan
  16. Pfizer, La Jolla, California, United States of America
  17. Princess Alexandra Hospital, Brisbane, Queensland, Australia
  18. University of Western Australia, Perth, Western Australia, Australia
  19. Tasman Health Care, Gold Coast, Queensland, Australia
  20. John Flynn Medical Centre, Gold Coast, Queensland, Australia
  21. Pfizer, New York, United States of America
  22. Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy

Background: BRAF/MEK inhibitor therapy has demonstrated PFS and OS benefits and is standard of care for the treatment of advanced BRAF V600-mutant melanoma. We report a 5-yr update from the COLUMBUS trial.

Methods: In Part 1 of COLUMBUS, 577 pts with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to encorafenib 450mg QD + binimetinib 45mg BID (COMBO450), encorafenib 300mg QD (ENCO300), or vemurafenib 960mg BID (VEM). An updated analysis including PFS, OS, ORR (by blinded independent central review), and safety was conducted after minimum follow-up of 65.2 m.

Results: At data cut-off (Sep 15, 2020), there were 131 (68%), 117 (60%), and 145 (76%) deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. For COMBO450, ENCO300, and VEM, the 5-year OS rate was 34.7%, 34.9%, and 21.4%, and median OS rates were 33.6, 23.5 and 16.9 months respectively (median follow-up: 70.4m). The 5-yr OS rate (95% CI) in COMBO450 pts who had normal LDH levels at baseline was 45.1% (36.5–53.2). For COMBO450, ENCO300, and VEM, the 5-year PFS rate was 22.9%, 19.3%, and 10.2%; ORR (95% CI) was 64.1% (56.8–70.8), 51.5% (44.3–58.8), and 40.8% (33.8–48.2); and the median duration of response (DOR) was 18.6, 15.5, and 12.3m, respectively. Safety results were consistent with the known tolerability profile of COMBO450. Additional efficacy and updated safety analyses will be presented. Following study drug discontinuation, the most common subsequent treatment in all arms was checkpoint inhibitors.

Conclusions: Updated OS and DOR COMBO450 results demonstrate continued long-term benefits in pts with BRAF V600-mutant melanoma. Clinical trial information: NCT01909453.