- 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.
- 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.
- 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).
- Open label.
- Early termination because of futility.