Clin Cancer Res: WEE1 kinase inhibitor adavosertib combined chemotherapy to treat TP53 mutant ovarian cancer.

Preclinical studies have shown that wee1 kinase inhibitor adavosertib makes TP53 mutant cells sensitive to chemotherapy.
Oza and others speculated that adavosertib combination chemotherapy could improve the efficacy of TP53 mutant ovarian cancer, and a randomized double-blind Phase II trial (NCT01357161) was conducted to verify this.
the trial recruited patients with platinum-sensitive ovarian cancer with TP53 mutations to be randomly assigned to the adavosertib group (225 mg, 2/day, oral, 21-day course of medication 2.5 days) or placebo group, all patients received carboptin (AUC5) and yew alcohol (175 mg/m2) until the disease progressed or was 6 courses of treatment.
end point is progress-free survival and safety.
121 patients were recruited, 59 in the adavosertib group and 62 in the placebo group.
adavosertib combination of chemotherapy extended the patient's enhanced RECIST v1.1 PFS (ePFS: medium value 7.9 vs 7.3 months; HR 0.63), meeting the expected significant threshold (p.lt;0.2).
compared to the placebo group, the incidence of adverse reactions was higher in the adavosertib group (diarrhea 75% vs. 37%, vomiting 63% vs. 27%, anemia 53% vs. 32%, and all level 3 adverse reactions 78% vs. 65%).
: Developing management tolerance and identifying the patient populations that benefit most from treatment may improve clinical benefits.
follow-up study should try to identify the most appropriate dosage and potential maintenance treatment options for adding adavosertib to the chemotherapy programme.
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