Kensuke Hori

Adjuvant Chemotherapy for Endometrial Cancer (ACE) trial: A randomized phase II study for advanced endometrial carcinoma

AbstractThis study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate‐risk stage I and II or high‐risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel‐epirubicin‐carboplatin (TEC), paclitaxel‐anthracycline (doxorubicin)‐carboplatin (TAC), or dose‐dense paclitaxel‐carboplatin (ddTC). The primary end‐point was the completion rate (CRate) of six cycles of treatment. The secondary end‐points were progression‐free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P = .005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2‐year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).

A phase II, open-labeled, single-arm study of dose-dense paclitaxel plus carboplatin in advanced or recurrent uterine endometrial cancer treatment: a KCOG-G1303, DOENCA trial

To determine the safety and efficacy of dose-dense (dd) paclitaxel (PTX) and carboplatin (CBDCA) in treating advanced or recurrent endometrial cancer. Women aged 20-75 years with histologically confirmed endometrial cancer, the International Federation of Gynecology and Obstetrics (FIGO) stage III disease with some residual tumor, FIGO stage IV disease, recurrence after front-line curative treatment, or recurrence after second-line chemotherapy or radiotherapy were enrolled in this study. PTX (80 mg/m²) was administered intravenously (IV) to every participant on days 1, 8, and 15, and CBDCA (area under the curve of 5) was administered IV on day 1 once every 3 weeks until the disease progressed, unacceptable adverse events occurred, or consent was withdrawn. The primary endpoint was the response rate (RR), while the secondary endpoints were progression-free survival, overall survival, and adverse effects. Forty-eight participants were enrolled, and 46 were eligible to receive treatment. The patients' median age was 61 years (range, 43-76 years). Twenty-two participants had experienced recurrence, and the remaining patients had primary advanced endometrial cancer. There were 10 cases of serous carcinoma, 3 cases of endometrioid carcinoma G3, 2 cases of carcinosarcoma, and 2 cases of clear-cell carcinoma according to histology. Twenty-nine participants (63.0%) received ≥6 cycles of chemotherapy. The RR (complete, 13 cases; partial, 20 cases) was 71.3% (95% confidence interval: 59.0%-84.5%). The dd PTX with CBDCA is feasible and available as a treatment option for advanced or recurrent endometrial cancer. UMIN Clinical Trials Registry Identifier: UMIN000017138.

Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study

To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified. ClinicalTrials.gov Identifier: NCT03759600.