Serous ovarian cancer: binimetinib fails phase 3

  • Monk BJ & al.
  • J Clin Oncol
  • 21 Aug 2020

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Binimetinib, a MEK inhibitor, failed to meet its primary endpoint of PFS in patients with low-grade serous ovarian cancer.
  • In exploratory analysis, KRAS mutation was associated with significant improvement in outcomes in patients who received binimetinib.

Why this matters

  • Further exploration is warranted to determine whether patients with KRAS mutation may derive greater benefit from binimetinib.

Study design

  • Phase 3 MEK Inhibitor in Low-Grade Serous Ovarian Cancer/ARRAY-162-311/ENGOT-ov11 study.
  • 303 patients with low-grade serous ovarian cancer were randomly assigned 2:1 to binimetinib or physician’s choice of chemotherapy.
  • Funding: Array BioPharma.

Key results

  • Median PFS was 9.1 months with binimetinib and 10.6 months with chemotherapy (HR, 1.21 [95% CI, 0.79-1.86]; prespecified HR for futility).
  • In the binimetinib vs chemotherapy group:
    • Objective response rate, 16% vs 13%.
    • Median duration of response, 8.1 vs 6.7 months.
    • Median OS, 25.3 vs 20.8 months.
  • Grade ≥3 adverse event rates were 76% with binimetinib and 44% with chemotherapy.
  • In post hoc analysis:
    • KRAS mutation was also associated with prolonged PFS in patients treated with binimetinib (median, 17.7 vs 10.8 months; P=.006).
    • KRAS mutation was not associated with PFS benefit in the chemotherapy group (P=.502).
    • In the binimetinib group, KRAS mutation status was significantly associated with local best response (P=.004).

Limitations

  • Open label.
  • Early termination because of futility.