Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months.Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC.

Objective: Geriatric patients requiring gynecological surgery is increasing worldwide. However, older patients are at higher risk of postoperative morbidity and mortality, particularly cardiopulmonary complications. Laparoscopic surgery is widely used as a minimally invasive method for reducing postoperative morbidities. We compared the outcomes of open and laparoscopic gynecologic surgeries in patients older than 55 years. Methods: We included patients aged >55 years who underwent gynecological surgery at a single tertiary center between 2010 and 2020, excluding vaginal or ovarian cancer surgeries were excluded. Surgical outcomes were compared between the open surgery and laparoscopic groups, with age cutoff was set at 65 years for optimal discriminative power. We performed linear or logistic regression analyses to compare the surgical outcomes according to age and operation type. Results: Among 2,983 patients, 28.6% underwent open surgery and 71.4% underwent laparoscopic surgery. Perioperative outcomes of laparoscopic surgery were better than those of open surgery in all groups. In both the open and laparoscopic surgery groups, the older patients showed worse overall surgical outcomes. However, age-related differences in perioperative outcomes were less severe in the laparoscopic group. In the linear regression analysis, the differences in estimated blood loss, transfusion, and hospital stay between the age groups were smaller in the laparoscopy group. Similar results were observed in cancer-only and benign-only cohorts. Conclusion Although the surgical outcomes were worse in the older patients, the difference between age groups was smaller for laparoscopic surgery. Laparoscopic surgery offers more advantages and safety in patients aged >65 years.

Objective: The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation of poly(ADP-ribose) polymerase inhibitors into clinical practice. Methods: Retrospective data from patients diagnosed with EOC (high-grade serous EOC for Taiwan) between January 2014 and December 2018 with ≥12 months follow-up from diagnosis were analyzed descriptively. Survival was evaluated by Kaplan-Meier with two-sided 95% confidence interval (CI). Results: Of the 987 patients (Australia, 223; S.Korea, 513; Taiwan, 251), 98% received platinum-based chemotherapy (CT). In S.Korea and Taiwan 76.0% and 78.9% respectively underwent primary cytoreductive surgery; in Australia, 56.5% had interval debulking surgery. Bevacizumab was included in primary/maintenance therapy for 22.4%, 14.6% and 6.8% of patients in Australia, S.Korea and Taiwan, respectively. Patients receiving bevacizumab were high-risk (reimbursement policy) and achieved similar real-world progression-free survival (PFS) compared with CT only. Overall, the median real-world PFS (months; 95% CI) was similar across Australia (16.0 [14.63–18.08]), S.Korea (17.7 [16.18–19.27]) and Taiwan (19.1 [17.56–22.29]). Conclusion This study reveals poor prognosis despite differences in demographics and treatment patterns for patients with EOC across Asia-Pacific suggesting the need for biomarker-driven novel therapies to improve outcomes.

Objective: Management of heavily pre-treated platinum-resistant ovarian cancer remains a therapeutic challenge. Outcomes are poor with non-platinum, single-agent chemotherapy (CT); however, molecularly targeted anticancer therapies provide new options. Methods: This open-label, investigator-initiated, phase 2 umbrella trial (NCT03699449) enrolled patients with platinum-resistant ovarian cancer (at least 2 prior lines of CT and Eastern Cooperative Oncology Group 0/1) to receive combination therapy based on homologous recombination deficiency (HRD) and programmed death ligand 1 (PD-L1) status determined by archival tumour sample assessment. HRD-positive patients were randomised to either olaparib 200mg bid tablet + cediranib 30mg qd (arm 1) or olaparib 300mg bid tablet + durvalumab 1,500mg q4w (arm 2). HRD-negative patients were allocated to either durvalumab 1,500 mg q4w + pegylated liposomal doxorubicin (PLD) or topotecan or weekly paclitaxel (6 cycles; arm 3, those with PD-L1 expression) or durvalumab 1,500 mg q4w + tremelimumab 75mg q4w (4 doses) + PLD or topotecan or weekly paclitaxel (4 cycles; arm 4, those without PD-L1 expression). Arm 5 (durvalumab 1,500 mg q4w + tremelimumab 300mg [1 dose] + weekly paclitaxel [60 mg/m2 D1,8,15 q4w for 4 cycles] was initiated after arm 4 completed. The primary endpoint was objective response rate (ORR; Response Evaluation Criteria in Solid Tumours 1.1). Results: Between Dec 2018 and Oct 2020, 70 patients (median 57 years; median 3 prior treatment lines [range 2–10]) were treated (n=16, 14, 5, 18, and 17, respectively). Overall ORR was 37.1% (26/70, 95% confidence interval=25.9, 49.5); 2 achieved complete response. ORR was 50%, 42.9%, 20%, 33.3%, and 29.4%, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients, respectively. No TRAEs leading to treatment discontinuation and no grade 5 TRAEs were observed. Conclusion This study, the first biomarker-driven umbrella trial in platinum-resistant recurrent ovarian cancer, suggests clinical utility with biomarker-driven targeted therapy. All treatment combinations were manageable, and without unexpected toxicities.