5579 Background: Patients (pts) with platinum-resistant ovarian cancer (PROC) have a poor prognosis, and traditional cytotoxic drugs have limitations in efficacy and safety. Therefore, we are exploring the combination of utidelone capsule (UTD2), a novel oral microtubule inhibitor, with fruquintinib capsule (F), a tyrosine kinase inhibitor targeting VEGFR 1,2,3, for the treatment of platinum-resistant recurrent ovarian cancer. Methods: This study is an open-label and Simon two-stage phase II clinical trial, aiming to enroll 35 pts with platinum-resistant recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. All pts were high-grade serous ovarian cancer, with prior 1-5 lines of systemic therapy, and no more than 3 lines of subsequent therapy after platinum-resistant recurrence. Subjects received F in combination with UTD2 in 21-day cycles. The dose of F was 5 mg once daily, taken orally from day 1 to day 14 of each cycle. The dose of UTD2 was 60 mg/m²/day once daily, taken orally from day 1 to day 5 of each cycle. Primary endpoint was objective response rate (ORR) per RECIST v1.1. In Stage 1, 14 pts received per protocol treatment, and the study would proceed to Stage 2 (enrolling additional 21 patients) if ≥2 objective responses (CR/PR) were observed in Stage 1. Secondary endpoints included investigator-assessed progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), overall survival (OS) and Safety. Results: From March 18, 2025 to December 22, 2025, 19 pts were enrolled. Median age was 59 years (range, 44-68) with an ECOG PS score of 1. Median prior lines systemic therapy was 3 (range, 1-5) with 1, 2, 3, 4 and 5 lines for 4 pts (21.1%), 2 pts (10.5%), 6 pts (31.6%), 5 pts (26.3%), and 2 pts (10.5%), respectively. Median number of chemotherapy lines after platinum resistance was 1 (range, 0-3), with 0, 1, 2, or 3 lines of chemotherapy for 6 pts (31.6%), 6 pts (31.6%), 5 pts (26.3%), and 2 pts (10.5%), respectively. 14 pts were evaluated for efficacy with an outcome of 1 complete response, 8 partial responses and 5 stable diseases. ORR was 64.3% (95% CI: 38.8-83.7) and DCR was 100%. Median PFS was 7 months (95% CI: 2.8-7.2) and median OS has not reached. The Grade 3 treatment-related AE (TRAE) included neutropenia (n=2), mucositis oral (n=1), palmar-plantar erythrodysesthesia syndrome (n=1), skin ulceration (n=1), diarrhea (n=1), pain (n=1) and neurotoxicity (n=1). There were no ≥Grade 4 TRAE. 1 patient discontinued UTD2+F due to TRAEs. Conclusions: Utidelone plus Fruquintinib demonstrated encouraging efficacy for the treatment of PROC with a tolerable safety profile. This study is still actively ongoing, and further data will be provided at time of presentation. Clinical trial information: NCT06973421 .

Endometrial cancer (EC) of no specific molecular profile (NSMP) subtype constitutes the majority of EC and shows significant heterogeneity. This study aims to explore the role of ARID1A mutation and protein expression in NSMP EC patients in a large Chinese cohort. A retrospective analysis was conducted on patients with NSMP EC who underwent primary surgery and next-generation sequencing (NGS). Clinicopathologic features, ARID1A mutation, protein expression and progression-free survival (PFS) were analysed in our study. A total of 547 patients were enrolled in the study, and 151 patients with NSMP were included in the final analyses. ARID1A mutations were identified in 49.0

Hysterectomy prevalence varies from 4 to 41

OBJECTIVE:Early-stage uterine leiomyosarcoma (uLMS) remains a clinical challenge due to high recurrence and mortality rates. As most early-stage cases are diagnosed at stage IB, this study aims to investigate the prognostic factors and optimal management for stage IB uLMS. METHODS:A retrospective review was conducted of medical records for patients who underwent surgical intervention and were diagnosed with stage IB uLMS at the Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center from January 1, 2006, to August 31, 2023. RESULTS:After a median follow-up time of 70.1 months (range: 2.3-234.1), we observed a median disease-free survival (DFS) of 18 months and overall survival (OS) of 67.9 months, respectively. Median DFS was 14.7 months in the observation group and 18.4 months in the adjuvant chemotherapy group. Median OS was 75.4 months in the observation group and 66.6 months in the adjuvant chemotherapy group. Five-year DFS rates were 14.1% and 15.7%, and OS rates were 66.5% and 54.1% for the observation and chemotherapy groups, respectively. Poor DFS was associated with age >48 years, postmenopausal status, tumor size >12 cm, elevated Ki-67 levels, and lymphadenectomy, but these factors did not correlate with OS outcomes. No significant DFS or OS differences were found between chemotherapy and observation groups or across chemotherapy regimens. Ovarian preservation did not affect prognosis. CONCLUSION:Age >48 years, postmenopausal status, larger tumor size, higher Ki-67, and lymphadenectomy predicted poor DFS but not OS in stage IB uLMS. Ovarian preservation is safe. Adjuvant chemotherapy with different regimens showed no significant survival benefits.

Ovarian cancer (OC) is a highly lethal gynecological cancer. Olaparib maintenance therapy was effective and well-tolerated in pivotal RCTs. However, nationwide real-world safety information is limited in China. This multicenter, prospective, observational drug intensive monitoring study monitored the safety of olaparib in a largest-to-date, real-world Chinese OC cohort. Eligible OC patients had received ≥ 1 dose of olaparib. Follow-up extended up to 30 days post-olaparib discontinuation or maximally for six months post-enrolment. Primary and secondary endpoints were adverse events (AEs) in all OC patients and in special populations (hepatically/renally impaired before olaparib treatment; aged > 65 years), respectively. By Jun 30, 2023, 799 patients from 33 sites were enrolled. By data cut-off (Dec 29, 2023), 796 patients treated with olaparib were analyzed. The median age was 55 years (range, 25–85). Of 796 patients, 490 (61.6

ObjectiveThe risk of lymph node metastasis significantly influences the choice of surgical strategy for patients with early-stage endometrial cancer. While sentinel lymph node dissection can be considered in clinically early-stage endometrial cancer, lymph node evaluation might be omitted in patients with very low risk of lymph node metastasis. This study aims to develop a predicting model for lymph node metastasis in these patients, identifying potential metastases as thoroughly as possible to provide clinicians with a preoperative reference that helps in decisions about surgical procedures and treatments.Materials and MethodsWe retrospectively collected data from 4,400 cases across two centers to develop a predictive model for lymph node metastasis in patients with early-stage endometrial cancer using a Fully-connected (FC) Network. Internal validation was performed, and an additional 750 cases were prospectively collected from subcenter 1 for external validation. After comparing commonly used imputation methods, missing values were filled using the K-Nearest Neighbors (KNN) for the highest sensitivity of the model. The model was evaluated by precision, sensitivity, specificity, and overall accuracy. The performance of the model was compared to other machine-learning models. The risk stratification was divided by 1%, 5%, and 25%. Combining the results of Logistic regression, the pathological subtype-specific nomograms were constructed and served as alternatives to the FC Network.ResultsThe FC Network achieved the highest sensitivity—0.982 in internal validation and 0.900 in external validation—demonstrating exceptional performance in identifying patients with probable lymph node metastasis compared to other machine-learning methods. Considering the prognostic implications of histological subtypes, subtype-specific nomograms were constructed, achieving AUCs of 0.810/0.784/0.834 for non-aggressive and 0.726/0.810/0.650 for aggressive subtypes across the training, internal, and external cohorts.ConclusionsThe model proposed in this study can be used for risk prediction of lymph node metastasis in early-stage patients. The nomograms can be used as a feasible and easily used alternative for the model.

ObjectiveTo evaluate the impact of depth of cervical stromal invasion (CSI) on the prognosis of International Federation of Gynecology and Obstetrics (FIGO) stage II endometrioid endometrial cancer (EEC).MethodsPatients with FIGO stage II EEC confirmed by postoperative histopathology and consecutively admitted to the Obstetrics and Gynecology Hospital of Fudan University and Fudan University Shanghai Cancer Center between 2008 and 2017 were included in this study and reviewed retrospectively.ResultsTwo hundred and ninety-seven patients were included in this study. There were 253 (253/297, 85.2%)patients with superficial (<50%) and 44 (44/297, 14.8%) cases with deep (≥50%) CSI. The median follow-up time was 75.0 months (range: 5-175 months). Patients in the ≥50% CSI group had a poorer prognosis compared to the <50% CSI group (recurrence-free survival [RFS]: adjusted hazard ratio [aHR] = 6.077, 95% Confidence Interval [CI]: 2.275-16.236, disease-specific survival [DSS]: aHR = 7.259, 95% CI: 2.546-20.695). Deep CSI was an independent predictor of local recurrence (aHR=5.537, 95% CI: 1.804-16.991). Post operative external beam radiation therapy (EBRT) was correlated with a reduced risk of recurrence (aHR = 0.288, 95% CI: 0.097-0.859).ConclusionDeep CSI is a poor prognostic factor for RFS and DSS in patients with FIGO stage II EEC. Postoperative EBRT can improve both RFS and DSS. Those findings imply that a detailed pathological report on the depth of CSI would be helpful in better understanding its impact on prognosis and selecting an appropriate postoperative treatment for the patient.

OBJECTIVE:Rare studies focused on patients with incidental diagnosis of endometrial cancer (EC) after hysterectomy. We intended to construct a prediction model of lymph node metastasis (LNM) based on Fully-Connected Network (FC Network) for these patients. METHODS:A total of 3,920 cases of EC that met the criteria from Obstetrics & Gynecology Hospital of Fudan University between January 2016 and February 2023 and 1995 cases from Fudan University Shanghai Cancer Center between January 2013 and October 2020 were retrospectively included for the construction of a predicting model which was based on FC Network. At the same time, 572 cases were prospectively collected for external validation. RESULTS:The sensitivity of the model was 0.946. Lympho-vascular space invasion, myometrial invasion, tumor grade, microcystic elongated and fragmented invasion, progesterone receptor, and cancer antigen 125 were used to construct a simplified nomogram. The area under the curve of the nomogram was 0.890 and 0.885 in validation and prospective cohorts, respectively. CONCLUSION:The model we proposed has good sensitivity and can be used to predict the risk of LNM in patients with incidentally found EC. The simplified nomogram can be used as a substitute in certain situations. Based on another study, the threshold of 5% and 25% can be used for risk stratification.

5516 Background: The first stage results of a Simon’s two-stage single-arm phase II trial showed promising antitumor activity and manageable safety of camrelizumab (a humanized anti-PD-1 monoclonal antibody) plus apatinib (a highly selective VEGFR2 inhibitor) in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy. Here, we report the primary results of this trial. Methods: This open-label, single-arm, phase II trial used a minimax Simon’s two-stage design. Patients with advanced or recurrent endometrial cancer that had progressed after at least one prior systemic therapy were treated with camrelizumab (200 mg, intravenously, every two weeks) and apatinib (250 mg, orally, daily) on a four-week cycle until disease progression or intolerable toxicity. The primary endpoint was the objective response rate per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Other assessed endpoints were disease control rate, time to response, duration of response, time to treatment failure, progression-free survival, overall survival, and treatment-related adverse events. Results: Between January 20, 2020 and October 14, 2022, 36 patients (median age: 60 [range: 29, 76] years; 17 [47.2%] had Eastern Cooperative Oncology Group [ECOG] performance status 1; 15 [41.7%] had received at least two prior systemic therapies) were enrolled. At the date of data cutoff (December 31, 2022), the median follow-up time was 13.9 (interquartile range: 5.8-23.2) months. All 36 patients were evaluable for efficacy, the confirmed objective response rate was 44.4% (95% CI: 27.9%, 61.9%) and the conformed disease control rate was 88.9% (95% CI: 73.9%, 96.9%), with two complete response, 14 partial response, and 16 stable disease. The median progression-free survival was 6.4 (95% CI: 5.2, 13.0) months. The treatment-related adverse events of grade 3 or greater occurred in 19 (52.8%) patients, with increased gamma-glutamyltransferase (8 [22.2%]), hyperglycemia (4 [11.1%]), hypertension (4 [11.1%]) and increased direct bilirubin (4 [11.1%]) being most common. Reactive cutaneous capillary endothelial proliferation occurred in 6 (16.7%) patients and all were grade 1 or 2. No treatment-related death occurred. Conclusions: Camrelizumab plus apatinib show promising antitumor activity and manageable toxicity in patients with advanced or recurrent endometrial cancer after failure of prior systemic therapy and warrant further investigation. Clinical trial information: ChiCTR2000031932 .

Abstract Objective The International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system for endometrial cancer (EC) was released with incorporating histology, lympho-vascular space invasion, and molecular classification together. Our objective is to further explore the clinical utility and prognostic significance of the 2023 FIGO staging system in China. Methods A retrospective analysis was conducted for patients who received standard surgeries and underwent genetic testing using multigene next-generation sequencing (NGS) panels between December 2018 and December 2023 at Fudan University Shanghai Cancer Center, Shanghai, China. The genomic and clinical data of all patients were analyzed, and stages were determined by both the 2009 and 2023 FIGO staging systems. Kaplan–Meier estimators and Cox proportional hazards models were used for survival analysis. Results A total of 547 patients were enrolled in the study. After the restaged by the FIGO 2023 staging system, stage shifts occurred in 147/547 (26.9%) patients. In patients with early stages in FIGO 2009 (stage I-II), 63 cases were rearranged to IAmPOLEmut and 53 cases to IICmp53abn due to the molecular classification of POLEmut and p53abn. Altogether 345 cases were in stage I, 107 cases in stage II, 69 cases in stage III, and 26 cases in stage IV according to the FIGO 2023 staging criteria. For stage I diseases, the 3-year PFS rate was 92.7% and 95.3% in 2009 and 2023 FIGO staging systems, respectively. The 3-year PFS of stage II in 2023 FIGO was lower than that of FIGO 2009 (3-year PFS: 85.0% versus 90.9%), especially in substage IIC and IICmp53abn. Three cases (12%) of stage IIIA in FIGO 2009 were shifted to stage IA3 FIGO 2023, with 3-year PFS rates of 90.9% versus 100%, respectively. In NGS analysis, the most prevalent gene alterations were observed in PTEN and PIK3CA. Conclusion The FIGO 2023 staging system was proved to be a good predictor of survival for EC patients with enhanced precision compared to FIGO 2009. Predominant stage shifts were observed in early-stage diseases. Distinct gene alterations of different subtypes may help to explore more accurate target therapies.

Dear Editor, Ovarian cancer remains the deadliest among all gynecological cancers. Although most patients at advanced stage respond to initial treatment, the majority experience recurrence [1]. It was estimated that 55,342 new cases and 37,519 deaths from ovarian cancer occurred in China annually [2]. Contemporarily, the treatment landscape has changed rapidly since the role of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) in ovarian cancer treatmentwas explored. Based on data from the PRIMA/ENGOT-OV26/GOG-3012 [3] and ENGOTOV16/NOVA trials [4], niraparib has been approved globally as maintenance therapy for newly diagnosed and platinum-sensitive recurrent ovarian cancer. The indication of niraparib for salvage treatment was based on the results of the QUADRA (NCT02354586) trial [5]. Although niraparib has been tested in prospective randomized clinical trials (RCTs), no multicenter study on its real-world application in China had been conducted. Considering the differences in population, accessibility and affordability of drugs, the results of the real-world settings may differ from those of RCTs. Therefore, we conducted this multicenter, non-interventional study at 8 hospitals. Datawere collected from electronic records of a prospective cohort of patients who initiated niraparib treatment between December 2018 and September 2021. The inclusion and exclusion criteria (Supplementary Figure S1) and the methodology are presented in Supplementary Materials and Methods. Of the total 142 patients, 93 received niraparib as first-line maintenance therapy, 31 as maintenance therapy for platinum-sensitive recurrent ovarian cancer, and 18 as salvage treatment. Themedian age was 57

e17614 Background: Compared with western countries, the application time of PARP inhibitor in China is shorter and the real world outcomes are affected by many factors. The objective of this study was to present the real-world patients’ portrait, and the results of Niraparib treatment in China. Methods: This study included 142 patients treated with Niraparib from 8 hospitals in China between Dec. 2018 and Sep. 2021. Patients’ characteristics were summarized. The efficacy and safety in first-line maintenance (1L-M), platinum-sensitive recurrence maintenance (PSR-M), and treatment for ovarian cancer were evaluated. Survival outcomes and the factors influencing PFS were estimated. Results: 93 patients received Niraparib as 1L-M, 31 as PSR-M and 18 as salvage. BRCA status was wild-type or unknown in 87.3% of patients. With a median follow-up time of 8.7m, the mPFS for 1L-M has not yet been reached, and the mPFS for PSR-M and salvage therapy was 10.5 months (95%CI: 3.9-NE) and 5.7 months (95%CI: 3.0-13.0), respectively. Responses to last chemotherapy (CR vs. PR, P= 0.0077) and CA125 value before taking Niraparib (≤35UI/ml vs. > 35UI/ml, P= 0.0344) were two important factors affecting PFS among 1L and PSR patients. 12.7%(18/142) of patients experienced grade ≥3 hematologic adverse events and 23.2% experienced dose adjustment. It was noteworthy that when the interval of chemotherapy and Niraparib < 21 days, the incidence of Grade ≥ 3 adverse events increased significantly ( P= 0.0355). Conclusions: This was the first and largest observational multicenter study reporting the outcomes of Niraparib treatment for ovarian cancer in real-world setting in China. Generally, Niraparib was effective and well tolerated, which was consistent with the results of prospective trials. However, in real world, it was more inclined to use Niraparib in late-line treatment without genetic testing.

Background: Apatinib, a small-molecule tyrosine kinase inhibitor that selectively targets vascular endothelial growth factor receptor-2, has clinical activity in recurrent/advanced gynecological cancers. However, its efficacy in uterine malignancy remains unclear. This study aimed to determine the efficacy and safety of single-agent apatinib in patients with recurrent uterine malignancy. Methods: This is a prospective single-center, single-arm, phase 2 study that enrolled patients aged 18-70 years with histopathologically confirmed recurrent endometrial cancer (EC) and recurrent uterine sarcoma (US), received at least 2 chemotherapy regimens, and an Eastern Cooperative Group performance status of 0-1. Apatinib (500 mg) was administered orally once daily. A treatment cycle was defined as 4 weeks. The patients were followed up every 2 cycles for tumor radiological assessment until disease progression. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded throughout the treatment and within 30 days of the last study treatment and graded as per the National Cancer Institute Common Toxicity Criteria Version 4.0. Results: A total of 33 patients (22 with EC and 11 with US) were enrolled between October 2018 and April 2021. Median follow-up duration was 11.7 months (interquartile range: 6.8-32.5 months). The patients received apatinib for a median of 4.79 cycles (range 2-13 cycles). In the EC and US cohorts, the ORRs were 27.2% [95% confidence interval (CI), 10.7% to 50.2%] and 9.1% (95% CI, 0.2% to 41.3%), the median PFS were 4.4 months (95% CI, 4.2 to 6.7 months) and 7.0 months (95% CI, 3.2 to 11.6 months), and the median OS were 11.7 months (95% CI, 6.8 months to not reached) and 18.1 months (95% CI, 9.2 months to not reached), respectively. The most common treatment-related AEs of all grades were hypertension (36.4%), proteinuria (33.3%), and hand-foot syndrome (30.3%). No treatment-related serious AEs or deaths occurred. Conclusions: To our knowledge, this is the first prospective study assessing the efficacy and safety of apatinib in patients with uterine malignancy. The results suggested that apatinib might be a potential treatment option for these patients.

OBJECTIVE:This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. METHODS:In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1-14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. RESULTS:33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5-17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand-foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4-5 events or deaths were observed. CONCLUSION:Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.

Background: In reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC. Methods: We retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model. Results: The study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration >= 9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births. Conclusions: Hysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.

5591 Background: For advanced or recurrent endometrial cancer (EC), therapeutic options remain scarce. Immune or antiangiogenic monotherapy has shown moderate efficacy in EC. Preclinical and clinical data showed that camrelizumab (an anti-PD-1 antibody) plus apatinib (a selective VEGFR2 inhibitor) markedly enhanced anti-tumor efficacy in multiple solid tumors. This study was designed to assess the efficacy and safety of the combination of camrelizumab and apatinib as second-line or above therapy for advanced or recurrent EC. Methods: This was an open-label, single-arm, phase II trial conducted in China. Patients with advanced or recurrent EC who progressed after at least first-line therapy received camrelizumab (200 mg, intravenously, q2w) plus apatinib (250 mg, orally, qd). Using a minimax Simon two-stage design, 21 patients were enrolled at stage I and if a complete or partial response was observed in at least four patients, the enrollment would be continued to 40 patients. The primary endpoint was the objective response rate (ORR) per RECIST version 1.1. Secondary endpoints included time to objective response (TTR), disease control rate (DCR), duration of Response (DoR), progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF) and safety. Here, the results of stage I are reported. Results: Between January 20, 2020 and July 8, 2021, 21 patients were enrolled. The median age was 57 years (range 29–72). Thirteen patients (61.9%) had ECOG PS of 0, and eight patients (38.1%) received at least two prior therapies. As of November 9, 2021, the median follow-up time was 13.5 months (IQR 11.3-16.3). Among 21 evaluable patients, the confirmed ORR was 47.6% (95% CI 25.7%-70.2%) with complete response in one patient (4.8%) and partial response in nine patients (42.9%); eight patients had stable disease for a DCR of 85.7% (95% CI 63.7%-97.0%). The median PFS was 11.8 months (95% CI 5.2-14.4). Treatment-related adverse events (TRAEs) of any grade and of grade ≥ 3 were reported in 21 (100%) patients and 10 (47.6%) patients, respectively. The most common grade ≥ 3 TRAEs included gamma-glutamyltransferase increased (six [28.6%]), direct bilirubin increased (four [19.0%]), alanine aminotransferase increased (three [14.3%]), aspartate aminotransferase increased (three [14.3%]) and hyperglycaemia (three [14.3%]). Four patients (19.0%) experienced reactive cutaneous capillary endothelial proliferation, all of which were grade 1-2. No treatment-related deaths were reported. Conclusions: Camrelizumab plus apatinib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced or recurrent EC after failure of at least first-line therapy. Clinical trial information: ChiCTR2000031932.

Objective:This study was aimed to profile hotspot exonuclease domain mutations (EDMs) of the DNA polymerase ϵ gene (POLE) in endometrial cancer (EC) and to investigate the effects of EDMs on tumor cell behavior and catalytic activities of Polϵ.Methods:POLE sequencing was performed in tumor tissue samples from patients with EC to identify hotspot EDMs. Bioinformatics tools were used to select the potential pathogenic EDMs. The association of EDMs with the clinical outcomes of patients was assessed. EC cells were transfected with wildtype POLE or POLE variants to examine the effects of the EDMs on EC cell behavior, including cell cycle, migration, and invasion. Co-immunoprecipitation was employed to obtain FLAG-tagged wildtype and mutant catalytic subunits of Polϵ, followed by the assessment of polymerase and exonuclease activities.Results:In addition to previously reported P286R and V411L, R375Q and P452L were identified as novel, and deleterious POLE hotspot EDMs of EC. Patients in EDM group had significantly better clinical outcomes than the rest of the cohort. Compared with wildtype POLE, overexpression of POLE variants promoted cisplatin resistance, G0/G1 cell cycle arrest, and cell migration and invasion in EC cells. Overexpression of POLE variants significantly increased the abundance of 3'-OH and upregulated the expression of DNA mismatch repair genes in HEK293T cells. Compared with wildtype Polϵ, Pol ϵ mutants exhibited undermined polymerase and exonuclease abilities in the presence of mismatched nucleotides in HEK293 cells.Conclusion:We characterized the of hotspot exonuclease domain mutations in the DNA polymerase ϵ gene and identified P286R, V411L, R375Q, and P452L as pathogenic POLE hotspot EDMs in endometrial cancer. These hotspot EDMs are associated with the malignant behavior of endometrial cancer cells in vitro and favorable prognosis in patients, suggesting that POLE affects a wide range of cellular processes beyond DNA replication and proofreading.

Objectives Treatment options for patients with recurrent endometrial cancer remain limited with few targeted drugs available for selected patients. Previous studies have shown synergistic antitumor activity of anlotinib, a tyrosine kinase inhibitor with niraparib, a PARP inhibitor in solid tumors. This study aimed to evaluate the efficacy and safety of niraparib with anlotinib for recurrent or metastatic endometrial cancer. Methods Patients with histopathologically confirmed recurrent or metastatic endometrial cancer, receiving at least one systemic chemotherapy were enrolled between February 2021 and April 2022. Patients were orally administered with niraparib 200 mg QD; anlotinib 12 mg QD from days 1–14 for 21-days until disease progression, death or intolerant toxicity. Primary endpoint was objective response rate (ORR) and secondary endpoint included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS) and safety. Results Out of 13 enrolled patients, 12 was evaluable for efficacy. The median age was 60 (range, 32–70 years) with a median follow-up time of 7.8 months. The complete response, partial response, stable disease and progression disease was achieved by 0%, 66.7%, 25.0%, 8.3% patients, respectively. The ORR and DCR was 66.7% and 91.7%, respectively. The median PFS was not reached. Most common any-grade treatment-related adverse events (TEAEs) were proteinuria (9[69.2%]), thrombocytopenia (4[30.8%]), leukopenia (4[30.8%]) and hypertension (4[30.8%]). Two patients had grade 3 TEAE of hypertension, one patient had grade 3 vomiting and anemia. Conclusions Niraparib combined with anlotinib showed promising efficacy and well tolerable safety in patients with recurrent, metastatic endometrial cancer.Clinical trial information: ChiCTR2000035853