Molecular markers of response of ENzalutamide in combination with PAClitaxel in a phase II trial for advanced or recurrent endometrioid endometrial adenocarcinoma (ENPAC)

ABSTRACT: We evaluated the efficacy of paclitaxel, carboplatin, and the androgen receptor (AR) inhibitor, enzalutamide, in a phase II study of advanced or recurrent endometrioid endometrial cancer and identified biomarkers associated with response to therapy. A safety lead-in study (part A) was performed in a small group of patients. The remaining patients (part B) received 160 mg of enzalutamide as a single agent before starting triplet therapy. Biopsies were obtained during the lead-in to evaluate molecular markers. Patients received carboplatin (AUC 5 IV Q3 weeks), paclitaxel (175 mg/m2 IV Q3 weeks), and enzalutamide (160 mg PO daily). Response was assessed every 3 cycles. Fifty-two patients were included (7 in part A and 45 in part B). Paired biopsies were collected for translational studies at two time points: prior to chemotherapy and after the first cycle of treatment, during which patients were receiving chemotherapy in combination with enzalutamide. No dose-limiting toxicities were observed during the safety lead-in. Among 40 evaluable patients, the objective response rate was 67.5% (95% CI, 50.9%–81.4%). The PFS duration was 13.27 months (95% CI, 10.58–25.49); the 6-month PFS probability was 0.79 (95% CI, 0.65-0.88). Mass spectrometry analysis of frozen tissues identified 43 significantly altered proteins (P<0.01) in the pre-treatment samples and 37 in the On-treatment samples between responders and non-responders. Responders had multiple AR-responsive genes enriched in the pre-treatment samples that were downregulated in the On-treatment samples. The combination of enzalutamide, carboplatin, and paclitaxel was tolerable and had promising clinical outcomes in patients with advanced or recurrent endometrioid endometrial cancer. Candidate biomarkers of response were identified and could contribute to further development. Clinical Trial registration number: NCT02684227.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296559 | GEO | 2026/01/01

REPOSITORIES: GEO