Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601.

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m 2 ), cisplatin (40 mg/m 2 ), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6-10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6-10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Prognostic significance of Ki67 during neoadjuvant chemotherapy in primary unresectable ovarian cancer.

AIM: The purpose of this study was to investigate whether the Ki67 values were associated with survival for predicting prognosis in patients with advanced ovarian cancer receiving neoadjuvant chemotherapy (NACT). METHODS: Among 17 patients treated with NACT, 13 patients were available for tissue samples from matched pre- and post-therapy tissues. Ki67 scores were transformed to a logarithmic scale for the statistical analyses. The optimal cutoff values of the log-phase Ki67 were assessed by receiver operating characteristic (ROC) analysis. Kaplan-Meier analysis, the log-rank test, and Cox regression analysis were carried out to analyze survival. RESULTS: The Ki67-decrease and post-NACT Ki67 were the independent factors associated with relapse-free survival (RFS) (p < 0.001 and p = 0.003). No association was observed on overall survival. The optimal cutoff values for the Ki67-decrease and the post-NACT Ki67 were 6.67% and 5.46 based on ROC where the area under ROC curves (AUC) were 1.00 (p < 0.001) with the 100% sensitivity and specificity. The median RFS was 537 days in patients showing Ki67-decrease >6.66% or post-NACT Ki67 level <5.46, while it was 224 days in those with Ki67 decrease ≤6.66% or post-NACT Ki67 level ≥5.46 (p = 0.001). CONCLUSIONS: The Ki67-decrease and the lower post-NACT Ki67 are independent factors associated with favorable RFS, indicating that they could be precise biomarker candidates for prognosis in NACT-administered patients with advanced ovarian cancer.