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Update on overall survival in COLUMBUS: A randomized phase III trial of encorafenib (ENCO) plus binimetinib (BINI) versus vemurafenib (VEM) or ENCO in patients with BRAF V600–mutant melanoma.
Journal article

Update on overall survival in COLUMBUS: A randomized phase III trial of encorafenib (ENCO) plus binimetinib (BINI) versus vemurafenib (VEM) or ENCO in patients with BRAF V600–mutant melanoma.

  • Liszkay, Gabriella Department of Dermatology, National Institute of Oncology, Budapest, Hungary;
  • Gogas, Helen Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece;
  • Mandalà, Mario Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy;
  • Arance Fernandez, ANA Maria Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Barcelona, Spain;
  • Garbe, Claus Department of Dermatology, University of Tübingen, Tübingen, Germany;
  • Schadendorf, Dirk Department of Dermatology, University Hospital Essen, Essen, Germany;
  • Dummer, Reinhard Department of Dermatology, University Hospital Zürich Skin Cancer Center, Zürich, Switzerland;
  • Ascierto, Paolo Antonio Melanoma Unit, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy;
  • Robert, Caroline Paris-Sud University, Gustave Roussy, Villejuif Cedex, France;
  • Pickard, Michael D Array BioPharma Inc., Boulder, CO;
  • Sandor, Victor Array BioPharma Inc., Boulder, CO;
  • Gollerkeri, Ashwin Array BioPharma Inc., Boulder, CO;
  • Flaherty, Keith Cancer Center, Massachusetts General Hospital, Boston, MA;
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Published in:
  • Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. 9512-9512
Cancer Research
Oncology
English 9512 Background: 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, as well as analyses of some prognostic subgroups, require long-term follow-up. Here we report an updated analysis of OS and other endpoints from the COLUMBUS trial. Methods: 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. Results: At data cutoff, there were 116, 113, and 138 deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. Across arms, median follow-up for OS was 48.6 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 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, 5.6–8.2). PFS was longer for COMBO450 vs VEM (HR, 0.52 [95% CI, 0.40–0.67). Landmark OS and PFS results, as well as subgroup analyses and updated safety and tolerability, will be presented. Conclusions: Updated PFS and OS results for COMBO 450 from the COLUMBUS trial continue to represent new benchmarks for combined BRAF/MEK-inhibitor combinations for treatment of BRAF V600‒mutated melanoma. Clinical trial information: NCT01909453.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/199000
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