Treatment Of Epithelial Ovarian Cancer Research Articles

Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer.

Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR-related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR-related PVs were examined. Kaplan-Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR-related. HRR-PV-positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR-PV-positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression-free survival. HRR-related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.

Sintilimab combined with bevacizumab in relapsed or persistent ovarian clear cell carcinoma (INOVA): a multicentre, single-arm, phase 2 trial

Ovarian clear cell carcinoma rarely responds to second-line chemotherapy, the recommended treatment for relapsed epithelial ovarian cancer. Here, we report the activity and safety of sintilimab in combination with bevacizumab in patients with relapsed or persistent ovarian clear cell carcinoma. In the prospective, multicentre, single-arm, phase 2 INOVA trial, patients aged 18-75 years with histologically confirmed relapsed or persistent ovarian clear cell carcinoma were enrolled from eight tertiary hospitals in China. Eligible patients had an Eastern Cooperative Oncology Group performance status score of 0-2 and previous exposure to at least one cycle of platinum-containing chemotherapy. Enrolled patients received sintilimab (200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks until disease progression. The primary endpoint was objective response rate assessed by independent central review based on Response Evaluation Criteria in Solid Tumours version 1.1. Eligible enrolled patients who received at least one cycle of treatment and had at least one tumour response assessment following the baseline assessment per protocol were included in the activity analysis. Patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04735861) and is ongoing. Between April 8, 2021, and July 3, 2023, 51 patients were screened and 41 patients received at least one dose of sintilimab in combination with bevacizumab. Response evaluation was completed in 37 patients. Objective responses were observed in 15 patients (objective response rate 40·5%; 95% CI 24·8-57·9), of which five (14%) were complete responses and ten (27%) were partial responses. At data cutoff (Jan 29, 2024), the median follow-up was 16·9 months (IQR 7·5-23·4). Three (7%) patients developed grade 3 treatment-related adverse events including one patient with proteinuria, one patient with myocarditis, and one patient with rash. No treatment-related adverse events of worse than grade 3 severity were recorded. Treatment-related serious adverse events occurred in two (5%) patients including one patient with immune-related myocarditis and another with hypertension and renal dysfunction. No treatment-related deaths occurred. Sintilimab in combination with bevacizumab showed promising anti-tumour activity and manageable safety in patients with relapsed or persistent ovarian clear cell carcinoma. Larger, randomised trials are warranted to compare this low-toxicity, chemotherapy-free combinatorial regimen with standard chemotherapy. National Key Technology Research and Development Program of China, National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Innovent Biologics. For the Chinese translation of the abstract see Supplementary Materials section.

Ultra-radical surgery versus standard-radical surgery for the primary cytoreduction of advanced epithelial ovarian cancer; long-term tertiary center experiences

ObjectiveTo compare overall survival (OS) and morbidity outcomes in patients with advanced epithelial ovarian/tubal/peritoneal cancer undergoing standard-radical (SR) and ultra-radical (UR) surgical procedures based on NICE classification. Study DesignThis retrospective study analyzed data from 282 patients with 2014 FIGO stage III-IV epithelial ovarian cancer operated on between January 2006 and January 2019. The study compared OS, progression-free survival (PFS), and morbidity between SR and UR surgeries. Parameters influencing OS, including preoperative, postoperative, and post-adjuvant chemotherapy CA-125 values, surgical procedures, post-surgical residual tumor, histopathological grade, and FIGO surgical stage, were assessed. ResultsOut of 282 patients, 256 met the inclusion criteria. SR surgery was performed in 48 %, and UR surgery in 52 %. The mean preoperative CA-125 value was 1200 ± 1914.83, decreasing to 240.32 ± 373.87 postoperatively. The mean follow-up period was 63.01 ± 47.56 months. UR surgery correlated with significantly higher postoperative complications (p < 0.001), histopathological grade (p = 0.023), FIGO stage (p < 0.001), three-year death rates, and overall mortality rates (p = 0.035). FIGO stage and total metastatic lymph nodes emerged as independent prognostic factors for overall and PFS. ConclusionIn the treatment of epithelial ovarian cancer, evaluating the extent of the tumor before the surgery and showing maximal effort to minimize the residual tumor volume instead of applying UR procedures as the first choice seems to be the most important factor that can affect survival.

Exploratory Analysis Of Epidemiological, Clinicopathological Characteristics And Prognostic Factors Of Stage IV Epithelial Ovarian Cancers: A Single Institutional Study In Chennai

Background: Ovarian cancer (oc) is the 3rd most common cancer (ca) in females in India (globocan 2020)1 , epithelial ovarian cancer consists of 90% of all oc. More than 70% of ovarian ca patients diagnosed at advanced stage due to its asymptomatic nature and insidious onset of the disease. Metastases(mets) remained a major cause of mortality in ovarian cancer patients. This study is being undertaken to identify prognostic and predictive factors associated with the survival of patients with metastatic ovarian cancer. Materials and methods: It is a retrospective study. Patients diagnosed with stage IV epithelial ovarian cancer (treatment naive), who attended the department of medical oncology, Govt Royapettah Hospital (GRH), Chennai during 2013- 2018 with regular follow up included. 5 years follow-up data collected till dec, 2023. Aim of this study is to identify the epidemiological, clinicopathological characteristics, treatment outcome and other prognostic factors predicting overall survival (os) and progression free survival (pfs) in patients with stage IV ovarian cancer. Results: In this study 85 patients with stage IV epithelial ovarian ca were analysed. In our study median os is 27 months, pfs is 13 months. Overall survival (os) rate at 2 years (yr)= 0.5647, overall survival (os) rate at 5 years = 0.105. Progression free survival (pfs) rate at 2 years = 0.1765, progression free survival (pfs) rate at 5 years = 0.0471. Kaplan Meier (KM) survival curves have shown response after 1 st line treatment, surgery vs no surgery, platinum sensitive recurrence have significant association with 2 year, 5 year os and pfs (p&lt;0.05). Hpe (high grade serous vs less common ovarian cancers) has showed significant correlation with 5 year survival (p&lt;0.05), univariate cox regression analysis has shown, number of mets (single site vs multiple site) significantly associated with improved 2 year survival (p=0.02) and pfs (p=0.005). Both univariate and multivariate analysis showed age (&lt;=56 vs&gt;56) as independent factor correlating with 5 year survival (p=0.02), (p=0.01), multivariate cox regression analysis showed pretreatment ca 125 is an independent variables for pfs (p=0.04). Conclusion: In our study KM survival curves have shown if patients could undergo cytoreductive surgery, had response after 1 st line treatment (surgery and chemo) , significant improvement in 2 year, 5 year os and pfs can be achieved, though not established in regression analysis. Recurrence rate remained very high in advanced stage, in our study KM survival curve has shown platinum sensitive recurrence has significantly better 2 year, 5 year os and pfs rate. Cox regression analysis showed patients with single site of mets have significantly better 2 year survival and pfs than patients with multiple site of mets. Pre treatment raised ca 125 found to be an independent factor which can predict poor pfs. Higher age is an independent factor found to impact 5 year os

Assessment of the efficacy and safety of anlotinib for the treatment of recurrent epithelial ovarian cancer

ObjectiveThe current research aims to evaluate the efficacy and safety of anlotinib, an orally administered small-molecular tyrosine kinase inhibitor (TKI), in the treatment of recurrent epithelial ovarian cancer (EOC).MethodsPatients with recurrent EOC subjected to treatment with anlotinib in Fourth Hospital of Hebei Medical University from 2020 to 2022 were included. The evaluation involved a thorough review of medical records, focusing on parameters such as the objective response rate (ORR), disease control rate (DCR), survival outcomes, and safety profile.ResultsThis study recorded 51 patients, with 26 patients undergoing anlotinib monotherapy. The median progression-free survival (PFS) was 4.0 months, whereas the median overall survival (OS) was not reached. Seven cases underwent a combined treatment of anlotinib with chemotherapy. Among them, two patients achieved partial response (PR), two were categorized as stable disease (SD), and three were identified as having progressive disease (PD). The ORR and DCR were 28.5% (2/7) and 57.1% (4/7), respectively. Additionally, 18 cases received anlotinib maintenance therapy, and the median PFS and the median OS were 7.0 months and 25.5 months, respectively. The most prevalent adverse effects included fatigue (38.6%), hypertension (27.3%), nausea and vomiting (25.0%) and hand-foot syndrome (25.0%).ConclusionAnlotinib demonstrated mild efficacy in the treatment of recurrent EOC, whether employed as monotherapy, chemotherapy-combined therapy, or maintenance therapy. The safety profile was proven manageable and well-tolerated, suggesting that anlotinib may emerge as a viable and novel treatment option for recurrent EOC.

Pan-immune-inflammation value: a new prognostic index in epithelial ovarian cancer

BackgroundEpithelial ovarian cancer (EOC) is one of the deadliest gynaecological malignancies worldwide. The aim of this retrospective study was to create a predictive scoring model based on simple immunological and inflammatory parameters to predict overall survival (OS) and progression-free survival (PFS) in patients with EOC.MethodsWe obtained 576 EOC patients and randomly assigned them to the training set (n = 405) and the validation set (n = 171) in a ratio of 7:3. We retrospectively evaluated the association between PIV and OS and PFS using a novel immunoinflammatory marker, according to the optihmal treshold of PIV, we divided the patients into two different subgroups, high PIV (PIV > 254.9) and low PIV (PIV ≤ 254.9). Pan-immune Inflammatory Value (PIV) was computed as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). Then developed a simple score prediction model based on several independent prognostic parameters using Cox regression analysis. We used receiver operator characteristic (ROC) curves, calibration plots, and decision analysis (DCA) curves to evaluate the performance of the model. Finally, we used Kaplan-Meier curves to ensure that the model could distinguish well between low- and high-risk groups.ResultsThere was a significant difference in survival outcomes between high PIV (PIV > 310.2) and low PIV (PIV ≤ PIV310.2) (3-year survival rates of 61.34% and 76.71%, respectively); 5-year OS, 25.21% and 51.14%, respectively; 3-year PFS, 40.90% and 65.30%; 5-year PFS, 19.33% and 39.73%, respectively). Column plots of OS and PFS were constructed using independent prognostic factors. In the training module, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.713, 0.796, 0.839, and 0.730, 0.799, 0.826, respectively.In the validation cohort, the 3-, 5-, and 10-year AUCs for OS and PFS column charts were 0.676, 0.803, 0.685, and 0.700, respectively, 0.754, 0.727. The calibration curves showed good agreement between predicted survival and actual observations. The decision analysis curves also showed that the current model has good accuracy and clinical applicability. 3-year OS was 61.34% and 76.71%, respectively; 5-year OS was 25.21% and 51.14%, respectively; 3-year PFS was 40.90% and 65.30%, respectively; 5-year PFS was 19.33% and 39.73%, respectively.ConclusionsWe constructed and validated a PIV-based nomogram to predict OS and PFS in EOC patients, with a view to helping gynaecologists converge on oncologists in their treatment and follow-up expertise in epithelial ovarian cancer.

The Thoracic Surgeon: “The Icing on the Cake” in the Treatment of Epithelial Ovarian Cancer

In patients with ovarian cancer, VATS should be used to exclude or confirm the presence of supradiaphragmatic disease and possibly remove it completely. The simultaneous use of laparoscopy and VATS allows for an accurate selection of patients to be sent, in a very short time, to primary surgery or neoadjuvant chemotherapy. Therefore the thoracic surgeon should be part of the multidisciplinary team in every ovarian cancer center

Stereotactic radiotherapy for managing ovarian cancer oligoprogression under poly (ADP-ribose) polymerase inhibitors (PARPi)

ObjectivePoly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety...

Secondary Cytoreductive Surgery in Relapsed Platinum-Sensitive Epithelial Ovarian Cancer: A Systematic Review of Randomized Controlled Trials.

Secondary cytoreductive surgery is a treatment option for relapsed platinum-sensitive epithelial ovarian cancer, but no clear indications are defined for the procedure. This systematic review aims to establish clear indications and compare outcomes versus standard-of-care chemotherapy. We conducted an electronic literature search across three databases and identified 2033 articles, including three phase 3 randomized controlled trials (RCT). The review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (no. CRD42022379817). Despite varying patient selection methods, surgery plus chemotherapy demonstrated significantly prolonged progression-free survival compared to chemotherapy alone. However, overall survival outcomes were inconsistent: while GOG-0213 did not show extended overall survival, recent studies with stricter defined criteria for surgery (SOC-1 and DESKTOP-III) reported improved overall survival with the addition of surgery. Morbidity and mortality rates were low, with no difference in quality of life between the surgery and no-surgery groups. In conclusion, cytoreductive surgery presents a promising option for recurrent epithelial ovarian cancer treatment. Nonetheless, well-defined selection criteria appear crucial for achieving increased overall survival compared to conventional treatment.

Asian American sub-ethnic disparities and trends in epithelial ovarian cancer diagnosis, treatment and survival

ABSTRACT Objectives Studies on ovarian cancer (OC) diagnosis, treatment and survival across disaggregated Asian sub-ethnic groups are sparse. Few studies have also conducted trend analyses of these outcomes within and across Asian groups. Methods Using logistic, Cox, and Joinpoint regression analyses of the 2000–2018 Surveillance, Epidemiology, and End Results (SEER) data, we examined disparities and trends in OC advanced stage diagnosis, receipt of treatments and the 5-year cause-specific survival across seven Asian sub-ethnic groups. Results There were 6491 OC patients across seven Asian sub-ethnic groups (mean [SD] age, 57.29 [13.90] years). There were 1583(24.39%) Filipino, 1183(18.23%) Chinese, and 761(11.72%) Asian Indian or Pakistani (AIP) patients. The majority (52.49%) were diagnosed with OC with at an advanced stage. AIP were more likely to have advanced stage diagnosis than other subgroups (ORs, 95%CIs: 0.77, 0.62−0.96 [Filipino]; 0.76, 0.60−0.95 [Chinese]; 0.71, 0.54−0.94 [Japanese]; 0.74, 0.56−0.98 [Vietnamese] and 0.66, 0.53−0.83 [Other Asians]). The Filipinos were least likely to receive surgery but most likely to undergo chemotherapy. Japanese patients had the worst 5-year OC cause-specific survival (50.29%, 95%CI: 46.20%−54.74%). Based on the aggregated analyses, there was a significantly decreased trend in advanced-stage diagnosis and an increased trend in receipt of chemotherapy. Trends in OC outcomes for several subethnicities differed from those observed in aggregated analyses. Conclusion In this cohort study of 6491 patients, OC diagnosis, treatment, survival, and trends differed across Asian American ethnic subgroups. Such differences must be considered in future research and interventions to ensure all Asian American subethnicities equally benefit from the advancements in OC care and control.

Niraparib as maintenance therapy in Japan: a retrospective observational study using a Japanese claims database.

Epithelial ovarian cancer (EOC) is the leading cause of female mortality in gynecologic malignancies, with a rising incidence in Japan. This study aimed to validate the treatment patterns and safety of niraparib as maintenance therapy for EOC following initial chemotherapy in clinical practice in Japan. Leveraging claims data between April 2008 and December 2022, this descriptive study comprised EOC-diagnosed patients receiving initial platinum-based chemotherapy, debulking surgery, and niraparib as maintenance therapy. Patient characteristics, prescription status, transfusion details, and laboratory data were assessed and reported as summary statistics and frequencies. Among 291 patients, the median age was 64.0 years and 94.5% received a 200-mg daily dose of niraparib. At week 12, 78.7% (229/291) continued niraparib treatment, 21.3% (62/291) discontinued, and 52.2% (152/291) required treatment interruptions. Of the 62 patients who discontinued treatment, 27 patients initiated subsequent EOC treatment within 12 weeks following niraparib discontinuation. Blood transfusions were needed in 10.3% (30/291), and of 55 patients with available laboratory data, 61.8% (34/55) had decreased platelet count <100,000/µL, 25.5% (14/55) had decreased hemoglobin level <8 g/dL, and 22.7% (5/22) had decreased neutrophil count <1,000/µL, meeting the criteria for treatment interruption. Among those with thrombocytopenia, 88.2% (30/34) were able to either resume or continue treatment. Niraparib demonstrated favorable tolerability in Japanese patients with advanced EOC, with effective management of thrombocytopenia through dose adjustments and supportive care, supporting its viability as post-chemotherapy maintenance therapy.

Lipid droplets: a candidate new research field for epithelial ovarian cancer.

Ovarian clear cell carcinoma (OCCC) is a histological subtype that constitutes approximately 20% of epithelial ovarian cancer cases in Asian countries, but has a relatively low incidence in Western countries. Meanwhile, clear cell renal cell carcinoma (ccRCC) is a major subtype of kidney cancer. OCCC and ccRCC resemble one another histologically and have clear cytoplasmic appearances. Studies have revealed some genetic similarities between OCCC and ccRCC. However, information regarding common biological background factors between these cancers remains scarce. For example, accumulation of cellular lipid droplets was shown to play a crucial role in ccRCC progression, while similar information is lacking for OCCC. In this perspective article, we propose that lipid droplets may be candidates for future exploration to better understand the common biological backgrounds between OCCC and ccRCC, potentially leading to subtype-specific treatment strategies. We further discuss the relationship between poly ADP-ribose polymerase inhibition treatment and lipid metabolism because this therapeutic strategy has attracted considerable attention as a treatment for epithelial ovarian cancer.

65P Chemotherapy response score (CRS) and efficacy of PARP inhibitor (PARPi) treatment in advanced epithelial ovarian cancer (AEOC)

65P Chemotherapy response score (CRS) and efficacy of PARP inhibitor (PARPi) treatment in advanced epithelial ovarian cancer (AEOC)

Efficacy and safety of luveltamab tazevibulin vs investigator’s choice of chemotherapy in patients with recurrent platinum-resistant ovarian cancer (PROC) expressing folate receptor alpha (FRα): The REFRaME-01 (GOG-3086, ENGOT-79ov, and APGOT-OV9) phase 2/3 study.

TPS5637 Background: The treatment of recurrent epithelial ovarian cancer remains a challenge, particularly for tumors with low to moderate expression levels of FRα. Luveltamab tazevibulin (luvelta) is an anti–FRα-targeting antibody-drug conjugate with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR=4), which induces cytotoxic and immunologic cell death. Luvelta was designed to treat multiple cancers with a broad range of FRα expression. Luvelta demonstrated preliminary antitumor activity in women with recurrent ovarian cancer, selected for FRα expression level of ≥25% at any intensity (tumor proportion score [TPS]). In PROC, this cutoff represents an estimated 80% of patients (pts). In a phase 1 study of luvelta in relapsed ovarian cancer, the overall response rate (ORR) was 37.5% with a median duration of response (DOR) of 5.5 months and a median progression-free survival (PFS) of 6.1 months. ORR was higher at 5.2 mg/kg compared with 4.3 mg/kg (43.8% vs 31.3%). The safety profile was manageable, with the most common grade ≥3 adverse events consisting of neutropenia, arthralgia, and anemia (Oaknin et al. J Clin Oncol 2023;41[16 suppl]:5508). These results support further investigation in pts with PROC whose tumors have a broad range of FRα expression. Herein, we describe a phase 2/3 pivotal study (REFRaME-01)of luvelta in this pt population. Methods: This randomized, global, open-label, 2-part phase 2/3 pivotal study has been designed to assess the efficacy and safety of luvelta vs investigator’s choice (IC) chemotherapy in pts with recurrent PROC expressing FRα (NCT05870748). Eligible pts are adults (≥18 years) with relapsed PROC, 1–3 prior lines of therapy (which must include bevacizumab), measurable disease, Eastern Cooperative Oncology Group performance status ≤1, and TPS for FRα expression ≥25% using Ventana validated IHC assay. Part 1 (phase 2) consists of a luvelta dose-optimization stage in which pts are randomized 1:1 to receive intravenous (IV) luvelta every 3 weeks (Q3W) at 4.3 mg/kg or IV luvelta Q3W at 5.2 mg/kg with prophylactic G-CSF for 2 cycles followed by 4.3 mg/kg luvelta from cycle 3 onward. Part 1 data will be used to select the optimal dosing regimen. In part 2 (phase 3) ~550 pts will be enrolled and randomized 1:1 to the optimal luvelta dosing regimen or IC chemotherapy (gemcitabine, paclitaxel, pegylated liposomal doxorubicin, or topotecan). Primary endpoints are PFS and ORR, with response evaluated per RECIST v1.1. Secondary endpoints include overall survival, DOR, safety, and quality of life. Clinical trial information: NCT05870748 .

Efficacy and safety of niraparib in platinum-sensitive recurrent ovarian cancer: retrospective observational study in a tertiary hospital.

Niraparib has been authorized for maintenance treatment of epithelial ovarian cancer after first-line treatment with platinum, in partial or complete response. To evaluate the effectiveness and safety of maintenance niraparib in platinum-sensitive recurrent ovarian cancer (PSROC) patients in a tertiary hospital. This retrospective observational unicentre study included women diagnosed with ovarian adenocarcinoma who received niraparib. Eligibility criteria encompassed women with PSROC, in response to platinum chemotherapy, and not previously treated with other PARPis. Data on demographics, comorbidities, BRCA mutation status, disease stage, treatment history and adverse events were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. A total of 33 patients were included, with a median age of 63.5 years. The majority of patients received niraparib at 200 mg/day based on Research on Adverse Drug Events and Report criteria. Median OS was 30 months (95% CI: 16.76-43.23), and median PFS was 8 months (95% CI: 2.48-13.52). Adverse effects were more frequent during the initial months of treatment, with most classified as CTCAE v5 grade 1-2. Dose reductions, interruption of treatment and discontinuations were observed due to haematologic toxicities primarily. This real-world study showed that maintenance niraparib in PSROC patients had effectiveness and safety profiles consistent with clinical trials and other observational studies. Median PFS and OS were comparable to previous reports, and most adverse events were manageable with dose modifications. The results support the use of niraparib as a maintenance therapy option in this patient population.

Preclinical efficacy of CBR-5884 against epithelial ovarian cancer cells by targeting the serine synthesis pathway

Reprogramming of the serine synthesis pathway (SSP) is intricately linked to the progression of epithelial ovarian cancer (EOC). CBR-5884, a selective small-molecule inhibitor targeting phosphoglycerate dehydrogenase (PHGDH), effectively impedes the de novo synthesis of serine within cancer cells. This study aimed to evaluate the inhibitory effect of CBR-5884 on EOC cells and delineate its specific mechanism, thereby proposing a novel therapeutic approach for treating EOC. The suppression of serine biosynthesis after CBR-5884 treatment was evaluated using RNA sequencing and a serine assay kit, and the results showed that CBR-5884 effectively downregulated serine biosynthesis in EOC cells, particularly those expressing high levels of PHGDH. In vitro studies revealed that CBR-5884 demonstrated significant antitumor effects and suppressed migration and invasion of EOC cells through down-regulation of the integrin subunit beta 4 (ITGB4)/extracellular signal-regulated kinase (ERK)/epithelial–mesenchymal transition signal axis. Additionally, CBR-5884 mitigated the stemness of EOC cells and heightened their sensitivity to chemotherapy. Moreover, in vivo studies revealed that CBR-5884 significantly delayed tumor growth, with histological analysis indicating the safety profile of CBR-5884. Finally, the patient-derived organoid (PDO) models were utilized to explore the preclinical efficacy of CBR-5884 against EOC cells, and the results unveiled that CBR-5884 impeded proliferation and downregulated the expression of ITGB4 in EOC PDO models. Our findings supports the anticancer properties of CBR-5884 in EOC cells exhibiting high PHGDH expression, manifesting through the suppression of proliferation, migration, and invasion, while enhancing chemotherapy sensitivity, suggesting that CBR-5884 holds promise as an efficacious strategy for the treatment of EOC.

Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations

Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing. To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile. This cohort study was a secondary analysis of the PAOLA-1 randomized clinical trial that compared olaparib plus bevacizumab with placebo plus bevacizumab as maintenance treatment in patients with advanced high-grade ovarian cancer after a good response to first-line platinum with taxane chemotherapy plus bevacizumab, irrespective of germline or tumor BRCA1/2 mutation status. All patients with available tumor DNA were included in the analysis. The current analysis tested for an interaction between BRCA-like status and olaparib treatment on survival outcomes. The original trial was conducted between July 2015 and September 2017; at the time of data extraction for analysis in March 2022, a median follow-up of 54.1 months (IQR, 28.5-62.2 months) and a total follow-up time of 21 711 months was available, with 336 PFS and 245 OS events. Tumor homologous recombination deficiency was assessed using the BRCA-like copy number aberration profile classifier. Myriad MyChoice CDx was previously measured. The trial was randomized between the olaparib and bevacizumab and placebo plus bevacizumab groups. This secondary analysis assessed hazard ratios (HRs) of olaparib vs placebo among biomarker strata and tested for interaction between BRCA-like status and olaparib treatment on PFS and OS, using Cox proportional hazards regression. A total of 469 patients (median age, 60 [range 26-80] years) were included in this study. The patient cohort consisted of women with International Federation of Gynaecology and Obstetrics stage III (76%) high-grade serous (95%) ovarian cancer who had no evaluable disease or complete remission at initial or interval debulking surgery (76%). Thirty-one percent of the tumor samples (n = 138) harbored a pathogenic BRCA mutation, and BRCA-like classification was performed for 442 patients. Patients with a BRCA-like tumor had a longer PFS after olaparib treatment than after placebo (36.4 vs 18.6 months; HR, 0.49; 95% CI, 0.37-0.65; P < .001). No association of olaparib with PFS was found in patients with a non-BRCA-like tumor (17.6 vs 16.6 months; HR, 1.02; 95% CI, 0.68-1.51; P = .93). The interaction was significant (P = .004), and HRs and P values (for interaction) were similar in the relevant subgroups, OS, and multivariable analyses. In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA-like tumor, but not those with a non-BRCA-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment.

Epithelial Ovarian Cancer: The Importance of Early Diagnosis and Individualized Treatment with Combination Chemotherapy and Targeted Therapy

Epithelial ovarian cancer is a malignant neoplasm that represents the majority of ovarian cancer cases. It is characterized by aggressiveness, often late diagnosis and therapeutic challenges. Early diagnosis is crucial to improving patients' survival rates and quality of life. Individualized treatment, combining chemotherapy and targeted therapy, has been a promising approach to optimize therapeutic results and minimize adverse effects. Objective: to analyze and synthesize the available evidence on the importance of early diagnosis and individualized treatment with combined chemotherapy and targeted therapy in epithelial ovarian cancer. Methodology: Using the PRISMA checklist, this review was conducted based on articles published in the last 10 years. The databases used were: PubMed, Scielo, Web of Science. The descriptors: "epithelial ovarian cancer", "early diagnosis", "individualized treatment", "combined chemotherapy", "targeted therapy". Inclusion criteria: original studies in humans, published in English or Portuguese, addressing the early diagnosis and/or individualized treatment of epithelial ovarian cancer. Exclusion criteria: animal studies, systematic reviews, studies with non-representative samples. Results: The results of this review highlight the importance of early diagnosis through imaging techniques and tumor markers. Furthermore, they highlight the effectiveness of combination chemotherapy, especially regimens containing platinum and taxanes, together with targeted therapy, such as PARP inhibitors, in improving response rates and survival in patients with epithelial ovarian cancer. Conclusion: Early diagnosis and individualized treatment with combination chemotherapy and targeted therapy play a key role in the management of epithelial ovarian cancer. This multifaceted approach can significantly improve patients' clinical outcomes and quality of life, highlighting the importance of personalized therapeutic strategies in this challenging clinical context.

Utility of CA-125 in interval surgery

Standard treatment for advanced-stage epithelial ovarian cancer (EOC) consists of debulking surgery and chemotherapy. Progression-free survival (PFS) and overall survival (OS) correlate with residual tumor burden after debulking surgery. There are situations in which it is not feasible to perform the aforementioned surgery, requiring neoadjuvant chemotherapy (NACT) with eventual interval surgery. The objective of the study was to retrospectively evaluate patients who were not plausible for primary cytoreduction, analyzing the value of CA-125 pre and post neoadjuvant chemotherapy and its suitability between these values and the surgical result.

Abstract 6657: Oncolytic Vaccinia Virus Carrying OPCML Tumor Suppressor is active in Epithelial Ovarian Cancer

Abstract Objective: Epithelial Ovarian cancer (EOC) has the highest mortality rate among gynecologic malignancies, necessitating novel therapeutic approaches. Viral oncolytic immunotherapy with recombinant oncolytic vaccinia virus (OVV) offers promise for advanced-stage cancer treatment. OPCML is a GPI-anchored 3 Ig-domain tumor suppressor inactivated by somatic methylation in 87% of EOC. OVV with OPCML (OVV-OPCML) gene insertion may have potential as a therapeutic agent. This study explores the oncolytic, signaling-inhibitory, anti-angiogenic and synergistic immunotherapeutic properties of OVV-OPCML in EOC treatment, evaluating its therapeutic potential. Methods: To create OVV-OPCML, the virulent vaccinia virus Copenhagen strain F3L site was modified with OPCML cDNA, confirmed by qPCR and western blot. Oncolytic potential was assessed through in vitro and in vivo EOC cell infection with OVV-OPCML. Real-time cell analysis (RTCA) assessed cell proliferation. Xenograft tumor models in nude mice were used to evaluate in vivo oncolytic activity, while OVV-OPCML combined with anti-PD-1 treatment was tested using a syngeneic orthotopic EOC mouse model (ID8) in C57BL/6 immunocompetent mice. Serum IFN-γ and TNF-α were quantified via ELISA. Receptor Tyrosine Kinases, angiogenesis and phosphorylation together with immune markers were examined by western blotting and by multiplex immunohistochemistry (mIHC) analysis of tumor sections. Results: OVV-OPCML selectively infected OC cells, leading to viral replication and tumor cell death, while sparing normal ovarian cells in-vitro. OPCML protein expression increased post-infection. OVV-OPCML reduced ERBB2, EGFR, and FGFR1 expression in SKVO3 OV cells. Intratumoral or intraperitoneal (IP) OVV-OPCML administration in human ovarian cancer nude mouse models reduced tumor growth and improved survival. IP in-vivo OVV-OPCML in combination with anti-PD-1 treatment in vivo, in the IP ID8 syngeneic model demonstrated synergy with survival improvement. H&amp;E staining showed tumor cell damage without significant harm to normal tissues. Protein expression of ERBB2, EGFR, FGFR1, and their phosphorylated forms decreased. CD31, VEGFR2, p-VEGFR2 (Tyr1175), and p-VEGFR2 (Tyr1214) downregulation suggested tumor angiogenesis disruption. OVV-OPCML treatment elevated serum TNF-α and INF-γ levels and increased CD8+ T cells and PD-L1 expression in OVV-OPCML treated syngeneic tumors. Conclusions: OPCML gene enhances OVV selectivity against OC cells through direct oncolysis and OPCML protein production, inhibiting specific RTKs, suppressing angiogenesis, and activating antitumor immune responses synergistically with anti-PD-1. OVV-OPCML therapy shows promise as a targeted strategy for ovarian cancer treatment. Citation Format: Yong Tang, Yingzhao Liu, Mingjing Deng, Fei Huang, Jiahu Wang, Paul Blake, Hani Gabra, Qi Wang. Oncolytic Vaccinia Virus Carrying OPCML Tumor Suppressor is active in Epithelial Ovarian Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6657.