Yoshiko Nanki

A prospective cohort study on the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer

Abstract Objective this prospective cohort study aimed to assess the safety and efficacy of bevacizumab combined with chemotherapy in Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer. Methods in this study, 40 Japanese patients with relapsed ovarian, fallopian tube or primary peritoneal cancer selected to receive bevacizumab with chemotherapy were enrolled. Patients in poor general condition were excluded. Each patient was monitored prospectively for adverse events, administration status, disease status and survival. Treatment was continued until intolerable adverse events or disease progression. The primary endpoint was safety. Results bevacizumab plus platinum-based chemotherapy was performed for 30 patients (median cycle; 16.5), while bevacizumab plus non-platinum chemotherapy was performed for 10 patients (median cycle; 5.5). Among bevacizumab-related adverse events, hypertension occurred in 80% of patients, proteinuria in 83%, mucositis in 25%, bleeding in 20%, thromboembolic events in 5.0% and fistula in 2.5%. Gastrointestinal perforation or other life-threatening lethal adverse events were not observed. Response rate and median progression-free survival were 73% and 19.3 months for patients with bevacizumab plus platinum-based chemotherapy, and 30% and 3.9 months for patients with bevacizumab plus non-platinum chemotherapy, respectively. There was no correlation between response rate and occurrence of adverse events such as hypertension or proteinuria. Conclusion bevacizumab combined with chemotherapy was tolerable and effective for Japanese patients with relapsed ovarian cancer, fallopian tube cancer or primary peritoneal cancer. Hypertension and proteinuria are frequently occurred and managed properly for continuing treatment.

Efficacy and safety of olaparib maintenance monotherapy for Japanese patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer

Olaparib maintenance therapy for platinum-sensitive relapsed ovarian cancer has been approved in Japan since April 2018. Here, we report the experience administering this therapy in our hospital, with the aim of evaluating efficacy and safety in the Japanese population. The study included 52 patients with platinum-sensitive relapsed ovarian, fallopian tube, and primary peritoneal cancer. All patients started olaparib at a dose of 300 mg twice daily. Information about treatment efficacy and adverse effects was collected retrospectively from medical records. Median age was 58 years old (range: 33-80), and 82.7% of the patients were diagnosed with high-grade serous carcinoma. Sixteen patients (30.8%) possessed the BRCA1/2 pathogenic variant (15 germline and 1 tissue), 3 (5.8%) possessed variants of unknown significance (2 germline and 1 tissue), 16 (30.8%) possessed wild type, and 17 (32.7%) were not analyzed. Median progression-free survival was 15.3 months (95% CI 9.0-21.6). Patients with BRCA1/2 pathogenic variants showed significantly longer PFS than patients with wild-type BRCA1/2 (p = 0.007). Disease progression caused 34 cases to discontinue olaparib. Eighteen (34.6%) individuals exhibited ≥ grade 3 anemia, although they recovered in response to appropriate management. One patient discontinued olaparib because of prolonged renal dysfunction. Another patient presented with grade 3 fatigue, but recovered after 2 weeks of interruption and continued olaparib treatment. Olaparib maintenance therapy for platinum-sensitive recurrent ovarian cancer in the Japanese population is sufficiently safe and no less effective than reports from previous studies.