Recurrent Ovarian Cancer Patients Research Articles

The efficacy, safety, and beneficiary population of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer patients: A comparative cohort study.

Angiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer (RPR-OC) patients. This study retrieved 67 RPR-OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication. Objective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression-free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5-6.3) months in apatinib + chemo group and 3.8 (2.0-5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5-24.5) months in apatinib + chemo group and 13.6 (8.6-18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05). Angiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR-OC patients.

Weekly BH009 in patients with squamous cell carcinoma of the head and neck (SCCHN) and ovarian cancer: Interim phase I results.

e17545 Background: BH009 is a novel polysorbate 80-free formulation of docetaxel that will eliminate hypersensitivity reactions associated with polysorbate 80. BH009 has completed a bioavailability study compared to Taxotere and was found to have a better safety profile to Taxotere with the potential for higher doses. As a result, we conducted a phase I dose escalation study to determine the maximum tolerated dose (MTD), and the safety profile of a weekly BH009 regimen in the treatment of patients with advanced SCCHN and Ovarian cancer. Methods: This phase I study assessed safety of BH009 in patients with advanced SCCHN and Ovarian cancer. BH009 was administered at escalating doses (starting dose 40 mg/m2) as a 1-h i.v. infusion for three consecutive weeks every 28 days without dexamethasone premedication. Results: Up to January 2024, 11 patients were treated with BH009 (4 at 40 mg/m2, 7 at 50 mg/m2). 2 patients with SCCHN, and 9 patients with ovarian cancer. 100% of ovarian cancer patients were recurrent platinum-resistant ovarian cancer (PROC) patients. 82% (9/11) of patients had received prior taxanes, of whom 33% (3/9) had received prior docetaxel. There were no DLT observed in 40 mg/m2 dose groups, and one DLT was observed in the 50 mg/m2 group (grade 3 febrile neutropenia). The MTD for BH009 is expected to exceed 50 mg/m2, which would be higher than that of Taxotere under the same dosing regimen (≥50mg/m2 vs 42mg/m2*), and the overall tolerability was better than Taxotere. In this study, treatment-related adverse events (TRAEs) occurred in 100% (11/11) patients. The most common grade 3/4 TRAEs were Leukopenia (36%, n=4), Anaemia (36%, n=4), and Neutropenia (55%, n=6). Non-hematologic toxicities were generally mild with no grade 4 toxicity observed. No AEs that led to death were related to BH009. Up to January 2024, the DCR is 50% (3/6) after 2 courses of treatment. The ORR in 6 evaluable patients was 33% (2/6, 1 patient with SCCHN at 40 mg/m2, 1 patient with ovarian cancer at 50 mg/m2). One patient (17%, 1/6) with ovarian cancer at 50 mg/m2 dose group received a complete response to the target lesion and the non-target lesion was partially responded after 2 courses of BH009, and this patient had been previously treated with docetaxel, carboplatin, and bevacizumab. Conclusions: The weekly BH009 for three consecutive weeks every 28 days is a feasible schedule with a favorable toxicity profile, and the overall tolerability is better than Taxotere. BH009 has the potential to increase the dose of administration and improve the clinical efficacy. Dose escalation is ongoing. Clinical trial information: NCT06232863 . [Table: see text]

Comparison of target agent treatment strategies for platinum-resistant recurrent ovarian cancer: A Bayesian network meta-analysis.

We aimed to compare 7 newer immunotherapies and targeted therapies for platinum-resistant relapsed ovarian cancer. We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library electronic databases for phase III trials involving platinum-resistant recurrent ovarian cancer (PRrOC) patients treated with immunotherapy or targeted therapy in combination with chemotherapy. The quality of the included trials was assessed using the GRADE method. The primary outcome of comparison was progression-free survival, and secondary outcomes included overall survival and safety. This analysis included 7 randomized phase III controlled trials, encompassing 2485 PRrOC patients. Combining bevacizumab plus chemotherapy and lurbinectedin demonstrated statistically significant differences in progression-free survival compared to all other regimens of interest. However, no statistically significant differences were observed in the overall survival. Nivolumab and mirvetuximab exhibited fewer serious adverse events than the other regimens of interest. Our findings indicate that bevacizumab combined with chemotherapy and lurbinectedin monotherapy has significant efficacy in patients with PRrOC. For patients with PRrOC who have exhausted treatment options, nivolumab and mirvetuximab may be considered as alternatives because of their better safety profiles.

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.

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation

ABSTRACT Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

Sexuality as a Prognostic Factor-Results of an Individual Patient Data NOGGO (North-Eastern German Society of Gynecological Oncology)-Meta-Analysis of 644 Recurrent Ovarian Cancer Patients Prior to Chemotherapy.

The aim of this study was to analyze the associations between sexuality, quality of life, treatment discontinuation, and survival in recurrent ovarian cancer (OC). Raw data from various phase II/III studies, including the questionnaires EORTC-QLQ-C30 and QLQ-OV28, were included. Data from the meta-analysis were calculated using logistic and Cox regression. Data on sexuality were available for 644 patients. A total of 162 patients had an interest in sex and were sexually active (Group A). A total of 45 patients had an interest in sex and were sexually not active (Group I) and 437 patients had no interest in sex and were not sexually active (Group N). Group A was younger in median age (age at randomization), at 57 years, than Group I, at 60 years, and Group N, at 65 years (p < 0.001). Group A had a better ECOG performance status and fewer recurrences (all p < 0.001). FIGO stage, grading, and BMI were not associated with interest in sex and sexual activity. Group A showed higher scores in role, body, and social function (all p < 0.001), emotional functionality (p < 0.002), and body image (p = 0.012). In addition, Group A reported less pain, less peripheral neuropathy, and less fatigue (all p < 0.001). There was no association with the premature discontinuation of chemotherapy. Group A showed better survival rates compared to group N (22.3 months vs. 17.4 months, p < 0.001). Physicians should routinely address the topic of sexuality with ovarian cancer patients. Sexuality appears to be a marker for quality of life as well as overall survival.

Signatures of tumor-associated macrophages correlate with treatment response in ovarian cancer patients.

Ovarian cancer (OC) ranks as the second leading cause of death among gynecological cancers. Numerous studies have indicated a correlation between the tumor microenvironment (TME) and the clinical response to treatment in OC patients. Tumor-associated macrophages (TAMs), a crucial component of the TME, exert influence on invasion, metastasis, and recurrence in OC patients. To delve deeper into the role of TAMs in OC, this study conducted an extensive analysis of single-cell data from OC patients. The aim is to develop a new risk score (RS) to characterize the response to treatment in OC patients to inform clinical treatment. We first identified TAM-associated genes (TAMGs) in OC patients and examined the protein and mRNA expression levels of TAMGs by Western blot and PCR experiments. Additionally, a scoring system for TAMGs was constructed, successfully categorizing patients into high and low RS subgroups. Remarkably, significant disparities were observed in immune cell infiltration and immunotherapy response between the high and low RS subgroups. The findings revealed that patients in the high RS group had a poorer prognosis but displayed greater sensitivity to immunotherapy. Another important finding was that patients in the high RS subgroup had a higher IC50 for chemotherapeutic agents. Furthermore, further experimental investigations led to the discovery that THEMIS2 could serve as a potential target in OC patients and is associated with EMT (epithelial-mesenchymal transition). Overall, the TAMGs-based scoring system holds promise for screening patients who would benefit from therapy and provides valuable information for the clinical treatment of OC.

Secondary cytoreduction surgery for recurrent epithelial ovarian cancer patients after PARPi maintenance: A multicenter, randomized, controlled clinical trial

BackgroundPoly ADP-ribose polymerase inhibitors (PARPi) treatment has radically changed the treatment strategy for epithelial ovarian cancer. Cancer progression with PARPi maintenance is a new problem that has arisen in clinical...

CYTOKINE-MODULATING INFLUENCE OF HIPEC ON THE INTRAPERITONEAL HOMEOSTASIS FORMATION IN PATIENTS WITH OVARIAN CANCER

Background: Ovarian cancer (OC) has the greatest mortality rate among oncogynecological diseases. Most cases are diagnosed at the peritoneal dissemination stage, resulting in radical treatment. Most cases (75%) are diagnosed in III-IV stages at the stage of peritoneal dissemination, making the radical treatment impossible. Intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC), which has ceased to be an experimental technique over the past decade, is increasingly used among the methods of combating peritoneal carcinomatosis and demonstrates an increase in recurrence-free and overall survival in advanced stages of OC. Nevertheless, certain pathophysiological aspects of the effect of HIPEC on intra-abdominal homeostasis, and therefore on the further course of the disease, have not been elucidated. However, understanding this effect may be the key to the successful application of HIPEC and predicting its efficacy in each case of OC.&#x0D; Objectives: To access changes in intraperitoneal homeostasis in patients with advanced OC after HIPEC procedure (as a stage of cytoreductive surgery); in particular, to evaluate changes of TNF and TGF-β expression under the influence of HIPEC and systemic chemotherapy in the OC microenvironment.&#x0D; Materials and methods: The study included 33 OC patients treated at Lviv Regional Cancer Centre in 2016–2020. Twelve of them received HIPEC. The primary tumor cultures and primary cultures of peritoneal mesothelium and macrophages were obtained for all patients. The cytokines TNF and TGF-β activity were determined in their conditional media.&#x0D; Results: The decrease of TNF and TGF-β concentrations in the drainage exudate after HIPEC was revealed compared with the same parameters in the ascitic fluid before the operation. One-hour hyperthermia of the primary culture of peritoneal ascites-associated macrophages of recurrent OC patients decreased the TNF level in conditional media. A decline was found in 10 out of 12 cases.&#x0D; Conclusions: HIPEC has a cytokine-modulating effect on the intra-abdominal homeostasis of patients with OC, suppressing TNF expression by peritoneal macrophages. Reduced activity of TNF in supernatants of OC primary tumor cultures was associated with higher sensitivity to chemotherapy.

Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol

ObjectiveOvarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Study designPatients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. ConclusionThe results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.

Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer

ObjectivesThe aim of this study was to provide real-world efficacy and safety data on niraparib maintenance treatment in patients with non-germline (gBRCA)1/2 mutated platinum-sensitive recurrent ovarian cancer.MethodsThis retrospective multi-center cohort...

Prognostic Value of The Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Platelet Count for Platinum-Sensitive Recurrent Epithelial Ovarian Cancer.

To study the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and platelet count in patients with platinum-sensitive recurrent epithelial ovarian cancer (PS-ROC). This was a retrospective study on a database of platinum-sensitive recurrent epithelial ovarian cancer patients who received treatment at HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) between January 2010 and December 2020. The patients' demographic data, surgical factors, pathological factors, laboratory findings, and response to treatment were reviewed from the patients' medical records. Survival analysis was conducted using the Kaplan-Meier survival estimate and Cox regression model. In total, 56 patients were recruited in this study. The median overall survival (OS) and progression-free survival (PFS) were 33 (95%CI 23-43) and 11 (95%CI 8-16) months, respectively. Survival analysis showed a high PLR was associated with decreased OS compared with low value but no significant difference in PFS. High NLR was associated with poor OS and PFS. There was no association between the platelet count and survival outcome (OS and PFS). In the multivariable Cox regression analysis, the NLR, PLR, and platelet count were not significant prognostic factors for survival outcome. However, low hemoglobin and a decreased disease-free interval were significantly associated with poor PFS. A white blood cell count (WBC) ≥ 8,000 cells/mm3 was a poor prognostic factor for overall survival (Adjusted HR 7.64; 95%CI: 2.21-26.42; p-value = 0.001). The NLR, PLR, and platelet count were not associated with both the OS or PFS in patients with PS-ROC. However, the WBC level is an easy, readily available, and economical way to predict survival outcomes in PS-ROC patients and may help physicians to tailor therapeutic interventions in the future.

The accuracy of whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the detection of ovarian cancer relapse in patients with rising cancer antigen 125 (CA-125) levels

Background18F-fluorodeoxyglucose (FDG) PET/CT is a noninvasive imaging tool that has been used successfully for the diagnosis, staging, restaging, therapy monitoring, and prognostic prediction of ovarian cancer. For ovarian cancer surveillance, rising CA-125 levels raise the suspicion of recurrence despite its reported low specificity; being elevated in other benign and inflammatory conditions, and thus, confirmation is required. This work aimed to evaluate the role of 18F-FDG PET/CT in suspected ovarian cancer recurrence in patients presenting with elevated CA-125 levels.ResultsFifty female patients with suspected ovarian cancer recurrence owing to elevated CA-125 levels were included in this study. Recurrence was confirmed in 46/50 cases whether by histopathological confirmation or by serial follow-up imaging and clinical follow-up. Positive PET/CT findings were reported in 45/50 cases with 2 false-negative cases and 1 false-positive case. PET/CT examination was found to be superior to contrast-enhanced CT in the detection of peritoneal metastatic nodules and metastatic lymph nodes. According to this study, the estimated sensitivity, specificity, and overall diagnostic accuracy of PET/CT in the detection of recurrent ovarian cancer were 95.6%, 75%, and 94%, respectively.ConclusionsIn ovarian cancer surveillance, 18F-FDG PET/CT was found to be a sensitive and accurate noninvasive imaging tool that can be used in the detection of recurrent ovarian cancer in patients with elevated CA-125 levels, thus interfering with the management plan. The advantage of whole-body imaging in PET/CT allows for the detection and precise localization of recurrent or metastatic foci in abdominal and extra-abdominal sites as well.

Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design

Ovarian cancer (OC) is highly lethal due to late detection and frequent recurrence. Initial treatments, comprising surgery and chemotherapy, lead to disease remission but are invariably associated with subsequent relapse. The identification of novel therapies and an improved understanding of the molecular and cellular characteristics of OC are urgently needed. Here, we conducted a comprehensive analysis of primary tumor cells and their microenvironment from 16 chemonaive and 10 recurrent OC patient samples. Profiling OC tumor biomarkers allowed for the identification of potential molecular targets for developing immunotherapies, while profiling the microenvironment yielded insights into its cellular composition and property changes between chemonaive and recurrent samples. Notably, we identified CD1d as a biomarker of the OC microenvironment and demonstrated its targeting by invariant natural killer T (iNKT) cells. Overall, our study presents a comprehensive immuno-profiling of OC tumor and microenvironment during disease progression, guiding the development of immunotherapies for OC treatment, especially for recurrent disease.

Higher incidence of venous thromboembolism associated with increasing lines of chemotherapy in heavy treated recurrent ovarian cancer patients (054)

Higher incidence of venous thromboembolism associated with increasing lines of chemotherapy in heavy treated recurrent ovarian cancer patients (054)

Efficacy and safety of niraparib combined with anlotinib maintenance retreatment in platinum-sensitive recurrent ovarian cancer patients who previously received PARP inhibitor: An open-label, single-arm, prospective, exploratory phase II study (1265)

Efficacy and safety of niraparib combined with anlotinib maintenance retreatment in platinum-sensitive recurrent ovarian cancer patients who previously received PARP inhibitor: An open-label, single-arm, prospective, exploratory phase II study (1265)

Cost-effectiveness of maintenance niraparib with an individualized starting dosage in patients with platinum-sensitive recurrent ovarian cancer in China.

Objective: Niraparib improved survival in platinum-sensitive recurrent ovarian cancer (PSROC) patients versus routine surveillance, accompanied by increased costs. Based on the NORA trial, we evaluated for the first time the cost-effectiveness of maintenance niraparib with individualized starting dosage (ISD) in China. Methods: A Markov model was developed to simulate the costs and health outcomes of each strategy. The total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured. One-way and probabilistic sensitivity analysis were performed to estimate model robustness. Scenario analyses were also conducted. Results: Compared to routine surveillance, niraparib additionally increased QALYs by 0.59 and 0.30 in populations with and without germline BRCA (gBRCA) mutations, with incremental costs of $10,860.79 and $12,098.54, respectively. The ICERs of niraparib over routine surveillance were $18,653.67/QALY and $39,212.99/QALY. At a willingness-to-pay (WTP) threshold of $37,488/QALY, the ISD enhanced the likelihood of cost-effectiveness from 9.35% to 30.73% in the gBRCA-mutated group and from 0.77% to 11.74% in the non-gBRCA mutated population. The probability of niraparib being cost-effective in the region with the highest per capita Gross Domestic Product (GDP) in China was 74.23% and 76.10% in the gBRCA-mutated and non-gBRCA mutated population, respectively. Niraparib was 100% cost-effective for National Basic Medical Insurance beneficiaries under the above WTP thresholds. Conclusion: Compared to routine surveillance, the ISD of niraparib for maintenance treatment of PSROC is cost-effective in the gBRCA-mutated population and more effective but costly in the non-gBRCA mutated patients. The optimized niraparib price, economic status, and health insurance coverage may benefit the economic outcome.

Immune profile of primary and recurrent epithelial ovarian cancer cases indicates immune suppression, a major cause of progression and relapse of ovarian cancer

BackgroundOvarian cancer is the third most prevalent cancer in Indian women. Relative frequency of High grade serous epithelial ovarian cancer (HGSOC) and its associated deaths are highest in India which suggests the importance of understanding their immune profiles for better treatment modality. Hence, the present study investigated the NK cell receptor expression, their cognate ligands, serum cytokines, and soluble ligands in primary and recurrent HGSOC patients. We have used multicolor flow cytometry for immunophenotyping of tumor infiltrated and circulatory lymphocytes. Procartaplex, and ELISA were used to measure soluble ligands and cytokines of HGSOC patients.ResultsAmong the enrolled 51 EOC patients, 33 were primary high grade serous epithelial ovarian cancer (pEOC) and 18 were recurrent epithelial ovarian cancer (rEOC) patients. Blood samples from 46 age matched healthy controls (HC) were used for comparative analysis. Results revealed, frequency of circulatory CD56Bright NK, CD56Dim NK, NKT-like, and T cells was reduced with activating receptors while alterations in immune subsets with inhibitory receptors were observed in both groups. Study also highlights differential immune profile of primary and recurrent ovarian cancer patients. We have found increased soluble MICA which might have acted as “decoy” molecule and could be a reason of decrease in NKG2D positive subsets in both groups of patients. Furthermore, elevated level of serum cytokines IL-2, IL-5, IL-6, IL-10, and TNF-α in ovarian cancer patients, might be associated with ovarian cancer progression. Profiling of tumor infiltrated immune cells revealed the reduced level of DNAM-1 positive NK and T cells in both groups than their circulatory counterpart, which might have led to decrease in NK cell’s ability of synapse formation.ConclusionsThe study brings out differential receptor expression profile on CD56BrightNK, CD56DimNK, NKT-like, and T cells, cytokines levels and soluble ligands which may be exploited to develop alternate therapeutic approaches for HGSOC patients. Further, few differences in the circulatory immune profiles between pEOC and rEOC cases, indicates the immune signature of pEOC undergoes some changes in circulation that might facilitated the disease relapse. They also maintains some common immune signatures such as reduced expression of NKG2D, high level of MICA as well as IL-6, IL10 and TNF-α, which indicates irreversible immune suppression of ovarian cancer patients. It is also emphasized that a restoration of cytokines level, NKG2D and DNAM-1on tumor infiltrated immune cells may be targeted to develop specific therapeutic approaches for high-grade serous epithelial ovarian cancer.

Sexuality as a prognostic factor: Results of an individual participant data NOGGO-meta-analysis of 1,041 recurrent ovarian cancer patients before starting chemotherapy.

e24128 Background: Until now there is very little data available about sexuality in ovarian cancer patients. Aim was analyze if sexuality is associated with clinical parameters, quality of life, prior discontinuation of chemotherapy and survival in recurrent ovarian cancer patients before starting chemotherapy. Methods: Raw data including the QLQ-C30 and QLQ-OV28 EORTC questionnaire from four phase II/III trials (“Tower”, “Treosulfan”, “Hector” and “TRIAS”) conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) were synthesized for this individual participant data meta-analysis using ANOVA and cox regression analyses. All study participants were diagnosed with recurrent ovarian cancer and data for this analysis was gained before starting chemotherapy. Three patient groups were defined: (1) patients without interest in sex and not being sexually active, (2) patients with interest in sex and not being sexually active and (3) patients with interest in sex and being sexually active. Results: Data on sexuality was available from 644 patients with 437 patients without interest in sex and not being sexually active (1), 45 patients with interest in sex and not being sexually active (2) and 162 patients with interest in sex and being sexually active (3). Women of the third group were significantly younger with a median age of 57 years at randomization compared to women of group (1) with a median age of 65 years, p &lt; 0.001. Women with interest in sex and who were sexually active showed also a significant better ECOG performance status (p &lt; 0.001), had a lower number of recurrences (p &lt; 0.001) and had less frequently ascites at diagnosis (p &lt; 0.002). There were no differences regarding FIGO stage, BMI and grading between the three groups. Sexuality was associated with global quality of life (p &lt; 0.001) and physical, psychological, social, emotional and role functionality (p &lt; 0.001). Patients who were sexually active, reported less fatigue (p &lt; 0.001), less pain (p &lt; 0.001), less sleeping disorders (p = 0.004), less diarrhea (p = 0.008), less nausea and vomiting (p = 0.007) and less loss of appetite (p &lt; 0.001). There was no association with prior discontinuation of chemotherapy. Median overall survival (OAS) was 16.7 months in platinum-resistant patients being sexually active compared to a median OAS of 8.7 months in platinum-resistant patients who are not sexually active (p = 0.016). Conclusions: Medical personnel should routinely address sexuality in ovarian cancer patients as sexuality seems to be a marker for both QoL and overall survival and warrants further investigation.

Toxicity profile and discordance between patients/physicians regarding niraparib maintenance in recurrent ovarian cancer (ROC) patients: Lessons from the NIQOLE real-life study—GINECO study.

5521 Background: Niraparib (NI) maintenance is a standard of care in platinum-sensitive ROC. Based on pivotal randomized trials, toxicity profile appears manageable through adapted drug dosing. However, data on tolerance and feasibility for unselected patients (pts) are missing, especially regarding pts’ reported adverse events (AE). Methods: NIQOLE study is a real-life longitudinal multicenter, phase IV study in ROC pts treated with NI maintenance. NI starting dose was adapted to pts’ weight and platelet count. The primary endpoint was to describe physicians’ reported AE (NCI-CTC-AE, grading from 0 to 5) leading to treatment modifications (TM), defined by dose reduction or treatment interruption/discontinuation from baseline to month 3 and delay of first TM. Secondary endpoints included duration of treatment and pts’ reported AE. Progression rates were exploratory endpoints. Owing to a digital device, pts provided remoted weekly AE (NCI PRO-CTC-AE, grading from 0 to 3) which were accessible to investigators. Concordance between the main symptomatic AEs reported by pts and those reported by physicians was analyzed. Results: 139 pts were treated: median age 70 [44-88], high-grade serous histology 91%, BRCA mutation 5%, first relapse 72%, prior bevacizumab 71%. The median delay from platinum-based regimen and NI was 49 days [15-109]. NI starting dose was 200 mg in 80% of pts and the median treatment duration was 5.6 months [0.2-21]. Progression rates at 3 and 6 months were 19 and 45%, respectively. At 3 months, 60% (n=84%) of pts had at least one TM, of whom 47% (n=66) were treatment-related AEs: dose reduction in 17/66 (26%), interruption in 53/66 (80%) and discontinuation in 11/66 (17%). The first AE inducing TM occurred at 22 days (median) [2 -91]. Thrombocytopenia was the main AE leading to TM (70% of cases). 24% of AEs were grade 3-4. Remoted PRO-CTC-AEs were acknowledged by physicians in 59% of cases of whom 31% led to adaptation of pts’ care. During the 3 months, 98% of pts reported symptomatic AEs (including nausea, constipation, fatigue, dry mouth and insomnia), of which 66% were grade 3. There was a very poor correlation (&lt;0.20) between symptomatic AEs reported by the pts vs by the physicians (table). Conclusions: In real life, despite initial individual dosing, NI maintenance requires frequent TM during the first 3 months of treatment. There is a strong discrepancy between symptomatic AEs regularly captured by pts and those reported by physicians during clinics. Next generation of clinical trials should integrate pts' perspective to better assess toxicity and manage treatment course. Clinical trial information: NCT03752216 . [Table: see text]