OATH trial: a phase II trial evaluating the combination of onapristone with anastrozole for women with hormone receptor positive endometrial cancer

Background: The phase II Onapristone with Anastrozole for the Treatment of Hormone-receptor positive endometrial cancer (OATH) study aimed to evaluate the activity and safety of onapristone, a type 1 anti-progestin, in combination with anastrozole in patients with recurrent or metastatic hormone receptor positive endometrial cancer. The co-primary endpoints were objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria and progression-free survival. Secondary endpoints included disease control rate, duration of response, safety and tolerability, and quality of life assessments. Methods: This multicenter, open-label, prospective single-arm, phase II trial enrolled patients with hormone receptor positive (estrogen or progesterone receptor >1%) recurrent or metastatic endometrial cancer to receive onapristone 50 mg twice daily with anastrozole 1 mg once daily until disease progression or unacceptable toxicity. Results: As of December 2024, 14 patients were enrolled, with 13 pateints evaluable for at least one tumor assessment after baseline. One patient achieved a complete response, 2 patients achieved a partial response, 10 patients had stable disease, and one patient had progressive disease. The overall response rate was 21.4%, and the median progression-free survival was 14.2 months. The disease control rate was 92.9%. The duration of response for the patient with a complete response was 26.7 months, and the duration of response for the patients with partial responses was 23 and 6.5 months, respectively. The most common adverse events were grade 1 or 2 vasomotor symptoms (36%), transaminitis (29%), nausea (29%), and diarrhea (23%). No grade 4 adverse events or treatment-related deaths were observed. Conclusions: Onapristone combined with anastrozole in patients with pretreated, recurrent, or metastatic hormone receptor positive endometrial cancer shows promising activity in preliminary phase II results. Treatment is well-tolerated and offers a plausible therapeutic alternative for mismatch repair-proficient endometrial cancer patients with recurrent or metastatic disease. Clinical Trial Registration: NCT04719273.

Endometrial cancer; Hormone receptor positive; Hormonal therapy; Uterine cancer

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