Objective: This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence. Methods: JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved. Results: There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients’ backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24–0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS. Conclusion Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy.

Objective: This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence. Methods: JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved. Results: There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients’ backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24–0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS. Conclusion Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy.

Objective: This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence. Methods: JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved. Results: There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients’ backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24–0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS. Conclusion Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy.

Objective: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. Methods: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms “thrombocytopenia” and “platelet count decreased”) occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. Results: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56–1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6–26.7) months. Conclusion Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients.

Objective: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. Methods: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms “thrombocytopenia” and “platelet count decreased”) occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. Results: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56–1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6–26.7) months. Conclusion Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients.

Objective: This study evaluated the long-term safety and efficacy of niraparib in Japanese patients with platinum-sensitive recurrent ovarian cancer. Methods: This was a follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with platinum-sensitive, relapsed ovarian cancer. Participants received niraparib (starting dose 300 mg) once daily in continuous 28-day cycles. The primary endpoint was the incidence of Grade 3 or 4 thrombocytopenia-related events (defined as the overall incidence of the MedDRA Preferred Terms “thrombocytopenia” and “platelet count decreased”) occurring in the 30 days after initial administration of niraparib, and secondary endpoints included evaluation of treatment-emergent adverse events and progression-free survival. Results: Nineteen patients (median age, 62 years; median body weight, 53.9 kg) were enrolled. As previously reported, the incidence of Grade 3 or 4 thrombocytopenia-related events during the first 30 days of treatment was 31.6%. At data cutoff, median (range) treatment exposure was 504.0 (56–1,054) days and mean ± standard deviation dose intensity was 154.4±77.5 mg/day. The most common treatment-emergent adverse events were nausea (n=14, 73.7%), decreased platelet count (n=12, 63.2%), decreased neutrophil count (n=11, 57.9%), anemia, vomiting, and decreased appetite (all n=9, 47.4%). One patient was diagnosed with treatment-related leukemia, which resulted in death. Median (95% confidence interval) progression-free survival was 18.0 (5.6–26.7) months. Conclusion Overall, the safety profile of niraparib was considered manageable in this study population of Japanese patients with platinum-sensitive, relapsed ovarian cancer and was consistent with that observed in studies of non-Japanese patients.

Background: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutations in BRCA1/2, have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%–10% of BRCA1/2 alterations and 4%–6% of carcinomas of the uterine corpus, and 2.5%–4% of the uterine cervix have alterations of BRCA1/2. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052. Methods JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with BRCA1/2 mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with BRCA1/2 mutations (cohort A, C) and HRD positive uLMS without BRCA1/2 mutations (cohort B). Participants must have 1–3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16–20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate.

Objective: To assess the incidence of bevacizumab-associated gastrointestinal (GI) perforation during first-line treatment of patients with ovarian, fallopian tube, or peritoneal cancer receiving neoadjuvant chemotherapy (NAC) in Japanese real-world clinical practice. Methods: A retrospective study was conducted using a healthcare claims database owned by Medical Data Vision Co., Ltd. (study period, 2008–2020). Patients who initiated first-line treatment of ovarian, fallopian tube, or peritoneal cancer were identified and divided into NAC and primary debulking surgery (PDS) groups. The incidence of bevacizumab-associated GI perforation was compared within the NAC group and between the groups. Results: Paclitaxel + carboplatin (TC) was most commonly used as first-line treatment (39.5% and 59.6% in the NAC and PDS groups, respectively). TC + bevacizumab was used in 9.3% and 11.6% of patients in the NAC and PDS groups, respectively. In the NAC group receiving TC, the proportion of patients with risk factors for GI perforation was lower among patients with versus without concomitant bevacizumab. The incidence of GI perforation in the NAC group was 0.38% (1/266 patients) in patients receiving TC + bevacizumab and 0.18% (2/1,131 patients) in patients receiving TC without bevacizumab (risk ratio=2.13; 95% confidence interval [CI]=0.19 to 23.36; risk difference=0.20; 95% CI=−0.58 to 0.97). None of the 319 patients in the PDS group receiving TC + bevacizumab had GI perforation. Conclusion No notable increase was observed in GI perforation associated with NAC containing bevacizumab. We conclude that bevacizumab is prescribed with sufficient care in Japan to avoid GI perforation.

Objectives: This review aims to introduce preoperative scoring systems to predict lymph node metastasis (LNM) and ongoing clinical trials to investigate the therapeutic role of lymphadenectomy for endometrial cancer. Methods: We summarized previous reports on the preoperative prediction models for LNM and evaluated their validity to omit lymphadenectomy in our recent cohorts. Next, we compared characteristics of two ongoing lymphadenectomy trials (JCOG1412, ECLAT) to examine the survival benefit of lymphadenectomy in endometrial cancer, and described the details of JCOG1412. Results: Lymphadenectomy has been omitted for 64 endometrial cancer patients who met lowrisk criteria to omit lymphadenectomy using our scoring system (LNM score) and no lymphatic failure has been observed. Other two models also produced comparable results. Two randomized phase III trials to evaluate survival benefit of lymphadenectomy are ongoing for endometrial cancer. JCOG1412 compares pelvic lymphadenectomy alone with pelvic and para-aortic lymphadenectomy to evaluate the therapeutic role of para-aortic lymphadenectomy for patients at risk of LNM. For quality assurance of lymphadenectomy, we defined several regulations, including lower limit of the number of resected nodes, and submission of photos of dissected area to evaluate thoroughness of lymphadenectomy in the protocol. The latest monitoring report showed that the quality of lymphadenectomy has been well-controlled in JCOG1412. Conclusion Our strategy seems reasonable to omit lymphadenectomy and could be generalized in clinical practice. JCOG1412 is a high-quality lymphadenectomy trial in terms of the quality of surgical procedures, which would draw the bona-fide conclusions regarding the therapeutic role of lymphadenectomy for endometrial cancer.