BRAF+ CRC: triplet therapy shows OS benefit in phase 3 lead-in

  • Van Cutsem E & al.
  • J Clin Oncol
  • 20 Mar 2019

  • curated by Jim Kling
  • Univadis Clinical Summaries
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • Triplet therapy with binimetinib, encorafenib, and cetuximab was well-tolerated and achieved a median OS of 15.3 months in patients with metastatic BRAF V600E-positive colorectal cancer (CRC) who had failed 1 or 2 prior therapies.

Why this matters

  • Typical survival is 4-6 months in patients who have failed first-line therapies.
  • Authors write that the combination could become standard of care if supported in the randomized portion of the BEACON trial.

Study design

  • Safety lead-in to the phase 3 randomized, open-label BEACON trial.
  • Patients who had failed 1-2 previous regimens received binimetinib, encorafenib, and cetuximab (n=30).
  • Funding: Array BioPharma, Merck KGaA, Pierre Fabre Medicament, Ono Pharmaceutical. 

Key results

  • 5 patients experienced dose-limiting toxicities.
  • Toxicities: 2 grade 1 (6.7%), 7 grade 2 (23.3%), 16 grade 3 (53.3%), 5 grade 4 events (16.7%).
  • Treatment-emergent adverse events (TEAEs) included diarrhea (77%), dermatitis acneiform (67%), fatigue (63%), and nausea (63%).
  • Grade 3/4 TEAEs fatigue (13%), anemia (10%), increased aspartate transaminase (10%), increased creatine phosphokinase (10%), and urinary tract infection (10%).
  • In 29 patients with confirmed BRAF V600E-mutant tumors:
    • Centrally assessed overall response rate, 41% (95% CI, 23.5%-61.1%).
    • Median centrally assessed PFS, 5.5 (95% CI, 4.2-9.3) months.
    • Median OS, 15.3 (median follow-up, 18.2) months.

Limitations

  • Nonrandomized.
  • Small patient population.

Please confirm your acceptance

To gain full access to GPnotebook please confirm:

By submitting here you confirm that you have accepted Terms of Use and Privacy Policy of GPnotebook.

Submit