Platinum-sensitive Recurrence Research Articles

Experience of using chemotherapy treatment for the first recurrence of ovarian cancer

Background. The main goal of treating patients with recurrent ovarian cancer is to prolong life and improve its quality. Approaches to the treatment of recurrent ovarian cancer have changed over the past decade. The choice of antitumor drug therapy is determined by the duration of platinum-free interval and the use of targeted therapy with bevacizumab or olaparib. Treatment regimens for relapses are not unified and treatment outcomes are contradictory. Aim: to analyze treatment outcomes of different chemotherapy regimens in patients with the first recurrence of ovarian cancer, depending on the duration of platinum-free interval. Material and Methods. A retrospective analysis of the first recurrence of ovarian cancer in 446 patients treated at the Primorsky Regional Oncology Center in the period 2004–2021 was carried out. All patients were divided into two groups depending on the treatment option for relapse: repeated cytoreduction followed by chemotherapy or only second-line chemotherapy, and into four groups depending on the chemotherapy regimens: 1 – platinum and taxane agents; 2 – platinum and taxane agents with bevacizumab; 3 – platinum agents and non-taxane agents with bevacizumab; 4 – monotherapy with non-platinum agents with bevacizumab. Results. Significant advantages in progression-free survival after second-line chemotherapy (PFS-2) were observed in patients with platinum-resistant relapse after the 4th chemotherapy regimen. Patients with platinum-sensitive relapse had the best treatment outcomes after the 3rd chemotherapy regimen and repeated cytoreduction followed by chemotherapy with a platinum-free interval of 6–12 months and 12–24 months with any platinum-containing chemotherapy regimen. In the platinum-free interval of more than 24 months, significant benefits were observed with a combination of platinum and taxane agents + bevacizumab. In the group of patients without surgery, there were significant benefits in all three intervals when prescribing a combination of platinum and non-oxane agents ± bevacizumab. There was a tendency to increase PFS-2 in patients with low-grade serous ovarian carcinoma compared with patients with high-grade serous carcinoma. The best rates of relapse-free survival were noted with maintenance therapy with olaparib. Conclusion. In patients with localized recurrence of ovarian cancer and a platinum-free interval of more than 6 months, it is advisable to perform repeated cytoreduction followed by chemotherapy, taking into account the duration of the platinum-free interval. The administration of PARP inhibitors in the maintenance therapy of platinum-sensitive recurrence of ovarian cancer improves treatment results.

Impact of PARP inhibitors on progression-free survival in platinum-sensitive recurrent epithelial ovarian cancer: a retrospective analysis

ObjectivePoly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib and niraparib have shown promise in extending progression-free survival (PFS) in patients with platinum-sensitive recurrent (PSR) epithelial ovarian cancer. In this retrospective study, we aimed to present our own data on the effect of PARP inhibitors on PFS in recurrent epithelial ovarian cancer.Methods82 patients diagnosed with PSR epithelial ovarian, tubal, or primary peritoneal cancer between May 2017 and September 2023 were initially enrolled from our hospital. However, 16 patients had prior exposure to PARP inhibitors during primary treatment, and 11 were lost to follow-up. Consequently, the study focused on 55 eligible patients. PFS was compared between patients receiving PARP inhibitor maintenance therapy and those who did not.ResultsAmong the 55 patients with PSR epithelial ovarian cancer, 18 received olaparib as maintenance therapy, 19 received niraparib, and 18 opted for observation. PARP inhibitor therapy significantly extended PFS (mean 24.0 months) compared to observation (mean 9.0 months, p = 0.0005), regardless of BRCA mutation status (HR = 0.20, 95% CI: 0.08–0.50). Subgroup analysis showed no statistical difference between olaparib and niraparib. Additionally, there was no PFS difference based on BRCA mutation status within both PARP inhibitor groups.ConclusionOur retrospective study demonstrates that PARP inhibitor maintenance therapy, including olaparib and niraparib, significantly prolongs PFS in patients with PSR epithelial ovarian, tubal, or primary peritoneal cancer, These findings support the broad utilization of PARP inhibitors as a standard maintenance therapy for PSR epithelial ovarian cancer irrespective of BRCA mutation status.

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<0.05). Hpe (high grade serous vs less common ovarian cancers) has showed significant correlation with 5 year survival (p<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 (<=56 vs>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

TEDOVA: vaccine OSE2101 +/- pembrolizumab as maintenance in platinum-sensitive recurrent ovarian cancer.

Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ribose polymerase inhibitors, but these lines of therapy can only be used once in the disease course. Patients in first or second platinum sensitive relapse after poly ADP-ribose polymerase inhibitors and bevacizumab represent an area of unmet medical need. This academic sponsored, international Phase II randomized trial is evaluating the combination of a therapeutic cancer vaccine (OSE2101) with anti-PD1 (pembrolizumab) as maintenance therapy, in patients with platinum-sensitive recurrence regardless of number of prior lines and no progression after platinum-based chemotherapy.Clinical Trial Registration: NCT04713514 (ClinicalTrials.gov).

Efficacy of a platinum-based chemotherapy rechallenge for platinum-sensitive recurrence after PARP inhibitor maintenance

ObjectivePlatinum-free interval (PFI) is the period from the end of platinum-based chemotherapy to the date of recurrence. If the PFI is > 6 months, a platinum-based chemotherapy rechallenge is considered; however, its efficacy after poly adenosine 5′-diphosphate-ribose polymerase (PARP) inhibitor maintenance therapy is unknown. This study aimed to examine the efficacy of a platinum-based chemotherapy rechallenge after PARP inhibitor therapy. MethodsWe retrospectively evaluated patients with ovarian cancer with a PFI≥6 months with PARP inhibitor maintenance therapy, receiving platinum-based chemotherapy. Duration of PARP inhibitor therapy, best response to subsequent platinum chemotherapy rechallenge, and clinical characteristics were collected from medical records. Tumor response was assessed according to RECIST 1.1. Correlations were calculated using Spearman’s correlation coefficients. ResultsAmong the 10 included patients, seven (70 %) received PARP inhibitors after primary chemotherapy, and three (30 %) received chemotherapy for platinum-sensitive relapse. One and five patients harbored a germline BRCA1 and BRCA wild-type mutations, respectively, and two had homologous recombination proficiency. The median PFI was 303.5 (182–602) days, and PARP inhibitor therapy duration was 249 (147–570) days. Platinum chemotherapy rechallenge efficacy was complete and partial response and stable disease in one (10 %), six (60 %), and three (30 %) patients, respectively. The longer the duration of PARP inhibitor treatment, better the response to platinum agents (Spearman correlation coefficient 0.284, p = 0.0288). ConclusionPlatinum-based chemotherapy rechallenge is reasonable for patients with platinum-sensitive disease, using the traditional PFI cutoff of 6 months, even when the PFI is obtained with a maintenance PARP inhibitor.

Efficacy and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy with secondary cytoreduction for platinum resistant recurrent ovarian cancer: A single-center retrospective cohort study

Background/purposeThis retrospective study evaluated the efficacy and adverse effects of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) with secondary cytoreductive surgery (CRS) in patients with recurrent ovarian cancer. MethodsPatients diagnosed with recurrent epithelial ovarian cancer, including fallopian tube and peritoneal origin, who underwent oxaliplatin-based HIPEC with secondary CRS, were enrolled. The primary outcome was progression-free survival (PFS), and the secondary outcomes were overall survival (OS) and adverse events. ResultsA total of 33 patients were included in the analysis. The mean PFS and OS were 20.4 months (95% CI 16.3–24.5 months) and 26.7 months (95% CI 23.7–29.7), respectively. Furthermore, the OS and PFS between platinum-sensitive and resistant recurrence showed no significant difference. Univariate and multivariate analysis of PFS identified a pre-operative peritoneal carcinomatosis index (PCI) score of ≥5 as a poor prognostic factor. Among them, the incidence of acute kidney injury was 9.0 % & none had grade ≧3 adverse events. ConclusionOxaliplatin-based HIPEC with secondary CRS might provide a survival benefit for patients with recurrent ovarian cancer with a decreased incidence of renal toxicity compared to cisplatin-based regimens. It might be effective and feasible in selected recurrent ovarian cancer patients, regardless of platinum-sensitive or resistant.

Do all patients that undergo a ‘complete’ secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer, benefit from it?

Abstract Following the results of three randomized trials (GOG-213, DESKTOP-III, and SOC-1), secondary cytoreductive surgery (sCRS) is recommended as a therapeutic option for all patients with platinum-sensitive recurrence by the NCCN guidelines and for oligometastatic recurrence by the ESMO-ESGO guidelines. Criteria for predicting a complete gross resection (CGR) were used to select patients for sCRS in all three trials. No trial used surgical prognostic factors like disease sites or disease extent for stratification. The outcomes of sCRS varied in preplanned/post-hoc subgroup analyses. The survival following an incomplete CRS was worse than with systemic chemotherapy alone. Not all patients will benefit similarly from sCRS, even if a CGR is obtained. No trial evaluated the benefit of sCRS in patients receiving poly-ADP ribose polymerase (PARP) inhibitors. While GOG-213 showed no benefit of sCRS when bevacizumab was used, the role of bevacizumab in patients having a CGR was not evaluated. The use of targeted therapies during first-line therapy is increasing, affecting treatment decisions and future clinical trial designs. New trials on sCRS should stratify patients according to surgical prognostic factors; sub-group analyses should be performed only in patients with CGR.

Real-world TRAE association between niraparib and platinum-based chemotherapy.

Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated. Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher's exact test were used for correlation analysis. 1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified. 1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.

Platinum desensitization therapy and its impact on the prognosis of ovary high-grade serous adenocarcinoma: a real world-data.

To examine the value of five-step platinum desensitization therapy in epithelial ovarian cancer. A retrospective study was conducted on the high-grade serous adenocarcinoma of the ovary (HGSAO) patients who developed a platinum allergy during treatment and received desensitization therapy between January, 2016 and December, 2020. The logistic-regression was adopted to analyze the relationship between platinum desensitization therapy and prognosis in HGSAO patients. 92 HGSAO patients were included in the study. Among these, 35 patients (38.0%) experienced mild allergic reactions, 51 (55.4%) experienced moderate allergic reactions, and 6 (6.5%) experienced severe allergic reactions. The desensitization therapy was successful in 86 patients (93.5%). Six patients had desensitization failure, of which five experienced severe allergic reactions during desensitization. The logistic-regression analysis revealed no significant correlation between platinum desensitization therapy and progression-free survival (PFS) or overall survival (OS) of patients (P < 0.05). However, the subgroup analysis demonstrated that the success or failure of platinum desensitization therapy significantly impacted the OS of patients who were platinum-sensitive recurrence. The patients who had successful desensitization therapy had a superior OS. Five-step platinum desensitization therapy has potential application value in patients who were platinum-sensitive recurrence after first-line treatment but may bear the risk of severe allergic reactions.

Current treatment strategies for ovarian cancer in the East Asian Gynecologic Oncology Trial Group (EAGOT).

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT's multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Platinum-free Interval May Predict Duration of Maintenance Bevacizumab and Survival in Platinum-sensitive Recurrent Ovarian Cancer.

We investigated factors affecting the long-term duration of bevacizumab-based maintenance therapy (BMT) and survival in patients with the first platinum-sensitive recurrence of ovarian cancer (PSR). We included patients with the first PSR in two tertiary centers from January 2015 till August 2021. All patients received six cycles of paclitaxel, carboplatin, and bevacizumab followed by BMT. We collected data including age at recurrence, histologic types, the status of BRCA mutation, platinum-free interval (PFI), extent of secondary cytoreductive surgery (SCS), presence of extra-abdominal disease, numbers of recurred lesions, cycles of BMT, progression-free survival (PFS), and cancer-specific survival (CSS). The median cycles of BMT were 13 (range=1-108). A total 103 patients were included, who consisted of the short-term (<13 cycles; n=49; 47.6%) and long-term users of BMT (≥13 cycles; n=54; 52.4%). High-grade serous carcinoma (HGSC), PFI >12 months, and optimal cytoreduction during SCS were favorable factors for the long-term duration of BMT. Moreover, PFI >12 months and the long-term duration of BMT were factors for improved PFS, and HGSC and PFI >12 months were related to improved CSS. PFI >12 months may be associated with the long-term duration of BMT and improved survival in patients with the first PSR.

Prognosis Following Surgery for Recurrent Ovarian Cancer and Diagnostic Criteria Predictive of Cytoreduction Success: A Systematic Review and Meta-Analysis.

For women achieving clinical remission after the completion of initial treatment for epithelial ovarian cancer, 80% with advanced-stage disease will develop recurrence. However, the standard treatment of women with recurrent platinum-sensitive diseases remains poorly defined. Secondary (SCS), tertiary (TCS) or quaternary (QCS) cytoreduction surgery for recurrence has been suggested to be associated with increased overall survival (OS). We searched five databases for studies reporting death rate, OS, cytoreduction rates, post-operative morbidity/mortality and diagnostic models predicting complete cytoreduction in a platinum-sensitive disease recurrence setting. Death rates calculated from raw data were pooled based on a random-effects model. Meta-regression/linear regression was performed to explore the role of complete or optimal cytoreduction as a moderator. Pooled death rates were 45%, 51%, 66% for SCS, TCS and QCS, respectively. Median OS for optimal cytoreduction ranged from 16-91, 24-99 and 39-135 months for SCS, TCS and QCS, respectively. Every 10% increase in complete cytoreduction rates at SCS corresponds to a 7% increase in median OS. Complete cytoreduction rates ranged from 9-100%, 35-90% and 33-100% for SCS, TCS and QCS, respectively. Major post-operative thirty-day morbidity was reported to range from 0-47%, 13-33% and 15-29% for SCS, TCS and QCS, respectively. Thirty-day post-operative mortality was 0-6%, 0-3% and 0-2% for SCS, TCS and QCS, respectively. There were two externally validated diagnostic models predicting complete cytoreduction at SCS, but none for TCS and QCS. In conclusion, our data confirm that maximal effort higher order cytoreductive surgery resulting in complete cytoreduction can improve survival.

Efficacy of poly (ADP-ribose) polymerase inhibitors monotherapy and the impact to subsequent platinum-based chemotherapy in breast cancer susceptibility genes1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse

BackgroundThe therapeutic effect of poly (ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive in breast cancer susceptibility genes (BRCA)1/2-mutated ovarian cancer patients with secondary platinum-sensitive relapse.MethodsBRCA1/2-mutated patients with secondary platinum-sensitive relapse included in this study did not receive any maintenance regimen after first- and second-line platinum-based chemotherapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy without restriction. Progression-free survival (PFS) was defined as the time from third-line therapy to disease progression or death, PFS2 was defined as the time from platinum-based chemotherapy after PARPi resistance to next subsequent therapy or death. Post-recurrence survival (PRS) refers to the survival time after secondary platinum-sensitive relapse.ResultsA total of 119 patients were retrospectively analyzed, including 71 (59.7%) in study group and 48 (40.3%) in control group. The objective response rate (ORR: 77.5% vs. 80.0%, p=0.766) and PFS (median: 11.2 vs. 11.0 months, p=0.962) were comparable. The benefit of subsequent platinum-based chemotherapy after PARPi resistance was more pronounced in patients with PARPi treatment for more than 12 months (median PFS2: 8.6 vs. 4.3 months, p=0.040). PARPi monotherapy had no adverse effect on PRS compared with platinum-based chemotherapy (median PRS:41.2 vs. 42.8 months, p=0.323). Compared to patients in control group who had never received PARPi, PARPi monotherapy (median PRS: 41.2 vs. 33.7 months, p=0.019) and post-line treatment with PARPi in the control group (median PRS: 48.1 vs. 33.7 months, p=0.002) could prolong PRS for patients with secondary platinum-sensitive relapse.ConclusionsPARPi monotherapy was similar to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.

Triplet maintenance therapy of olaparib, pembrolizumab and bevacizumab in women with BRCA wild-type, platinum-sensitive recurrent ovarian cancer: the multicenter, single-arm phase II study OPEB-01/APGOT-OV4

In this multicenter, open-label, single-arm, Phase II study with Simon two-stage optimum design (NCT04361370), we investigate the efficacy and safety of triplet maintenance (olaparib, pembrolizumab, bevacizumab) in patients with platinum-sensitive recurrent ovarian cancer who are wild-type for BRCA 1/2. A total of 44 patients were enrolled, and the median follow-up duration was 22.9 months (interquartile range: 17.4–24.7). The primary outcome was 6-months progression-free survival (PFS), which was 88.6% (95% confidence interval [CI] 75.4–96.2), meeting the pre-specified primary endpoint. The secondary outcomes reported here include median PFS, 12-months PFS, and overall survival and safety. The median PFS was 22.4 months (20.4–∞), with a 12-months PFS rate of 84.0% (95% CI 69.3–92.0). The median overall survival was 28.6 months (27.3–∞). The combination demonstrated tolerable toxicity with manageable side effects. Other secondary outcomes include time-to-progression, time to subsequent treatment, time to second treatment and PFS2; however, this data is not reported, as treatment is still ongoing in a majority of patients. Exploratory analysis shows that patients who were homologous recombination deficiency-positive or had a programmed death-ligand 1 combined positive score ≥1 showed a favorable response (P = 0.043 and P < 0.001, respectively). Thus, triplet maintenance shows durable efficacy with tolerable safety in patients with platinum-sensitive recurrence.

Analysis of olaparib efficacy in patients with serous ovarian cancer

Modern treatment of ovarian cancer is impossible without understanding the carcinogenesis and the structure of malignant epithelial ovarian tumors and carrying out molecular genetic testing for homologous recombination deficiency. The choice of maintenance therapy depends on the presence of a mutation in the BRCA1/2 genes and the HRD status of the tumor. Targeted drugs, such as bevacizumab and olaparib, are used in the treatment of ovarian cancer. The aim of the work is to determine the effectiveness of olaparib in first-line maintenance therapy and in the treatment of platinum-sensitive recurrence of ovarian cancer. A retrospective study included 67 patients with high-grade serous ovarian cancer stages I–IV who were prescribed olaparib in first-line maintenance therapy or in maintenance therapy for the treatment of disease progression, provided a complete or partial response to platinum-containing chemotherapy in the period from 2016 to 2022. The median life expectancy of the patients receiving first-line maintenance treatment coincides with the median time to progression; only one patient died due to the progression of the disease, and the rest are alive. The median time to progression in the group of patients with maintenance therapy of relapses was 23.0 ± 1.5 months, and the median life expectancy was 24.7 ± 2.3 months. When comparing the patients of the first group, depending on the term of surgical treatment performed, the median life expectancy was statistically higher with primary cytoreduction and constituted 46.0 months, while in the interval cytoreduction group, it was 25.0 months (p = 0.018). When comparing the patients of the second group, depending on the mutation in the BRCA1 and BRCA2 genes, the median life expectancy was statistically higher in the patients with a mutation in the BRCA2 gene — by 38.6 months (p = 0.020). The addition of olaparib to the treatment of BRCA-associated ovarian cancer in first-line maintenance therapy and in the treatment of platinum-sensitive relapses of the disease makes it possible to increase the median time to progression and median life expectancy.

Real-world Efficacy and Safety of Bevacizumab for Advanced or Recurrent Müllerian Cancer: A Single-institutional Experience.

The efficacy and safety of bevacizumab for ovarian cancer have been reported in randomized phase III clinical trials. It is important to gather experience and data in a real-world setting. The objective of the present study was to evaluate the efficacy and safety of bevacizumab for patients with ovarian cancer in a real-world setting. For front-line settings, patients with FIGO stage III-IV ovarian cancer treated using bevacizumab and chemotherapy after debulking surgery (Chemo + Bev group, n=79), in addition to those treated with only chemotherapy after debulking surgery (Chemo group; n=66), at our institute were reviewed retrospectively. For recurrent settings, patients with recurrent ovarian cancers treated with bevacizumab and any chemotherapy were reviewed retrospectively (n=65). In the front-line setting, the disease-free survival was significantly longer in the Chemo + Bev group compared with that in the Chemo group (p=0.021). Hypertension and proteinuria were found to be statistically more frequent in the Chemo + Bev group compared with that in the Chemo group (p=0.002 and p=0.004). In the recurrent setting, in platinum-sensitive patients, the response rate (RR) and the disease control ratio (DCR) were 78.4 and 94.1%, respectively. In platinum-resistant patients, the RR and the DCR were 28.6 and 57.1% respectively. The median progression-free survival was 18.3 and 7.1 months for platinum-sensitive recurrence and platinum-resistant recurrence, respectively. The major ≥ grade 3 adverse event was neutropenia. The present study provided encouraging real-world evidence of the efficacy and safety of bevacizumab for ovarian cancer in real-world.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

Combination therapy of oral cyclophosphamide and bevacizumab for patients with recurrent ovarian and peritoneal cancer.

Chemotherapy for patients with recurrent cancer aims to obtain survival benefits, relieve symptoms, and improve quality of life. We used oral cyclophosphamide and bevacizumab (BEV) combination therapy in recurrent ovarian and peritoneal cancer cases, where standard chemotherapy was infeasible. Subsequently, we evaluated the safety and efficacy of this treatment. Between August 2014 and June 2020, patients received the following regimen: oral cyclophosphamide 50 mg daily and intravenous cyclic BEV 15 mg/kg every 3 weeks. Data from 2 facilities were retrospectively analyzed. Twenty-two patients were enrolled (20 with ovarian cancer and two with peritoneal cancer). The median follow-up period and age were 18.9 months (range, 5.0-51.5) and 60 years (range 37-81), respectively. Sixteen patients had platinum resistance. The median number of previous chemotherapy regimens was 2.5 (range 0-5). The median implementation cycle was five (range 2-14). Eighteen patients discontinued treatment due to side effects (3 patient) and disease progression (15 patient). Grade 2 toxicities included neutropenia (1 patient), proteinuria (1 patient), hypertension (2 patient), and esophagitis (1 patient). Two patients had complete response and one had a partial response. Five patients had stable disease. The response rate in platinum-sensitive recurrence was 33.3%, and 7.1% in platinum-resistant recurrence, and a clinical benefit was found in 8 (36.3%) patients. The median PFS and overall survival from cyclophosphamide and BEV initiation was 5.3 months (range, 0.8-23.5) and 9.2 months (range, 4.8-51.5), respectively. The combination of oral cyclophosphamide and BEV does not have a high response rate, but is well-tolerated and can be used safely in patients who are difficult to treat after second-line chemotherapy. Data from 2 facilities were retrospectively analyzed.

52P Real-world data of niraparib in platinum sensitive relapsed ovarian cancer: A multicenter experience of the MITO group

PARP (poly ADP–ribose polymerase) inhibitors are approved as maintenance therapy in platinum sensitive ovarian cancer (OC), in first line and in the recurrent setting, regardless BRCA mutational status. Real-world data after the introduction of these agents are needed to evaluate whether the benefit observed in phase III trials can be translated into clinical practice. The aim of our study was to provide real-life data on efficacy and safety of niraparib administered as maintenance in platinum sensitive relapsed OC patients (PSROC). This retrospective/prospective multicenter study included relapsed OC patients treated in 17 MITO centers and receiving niraparib as maintenance, according to the label, at the time of first or subsequent platinum sensitive recurrence. Clinical data at the time of diagnosis and at the time of recurrence before Niraparib treatment were collected from the patients´ medical records at each institution, centralized into an electronic CRF at the coordinating center (Fondazione Policlinico Gemelli) and analyzed. The efficacy and safety analysis, as primary objectives, was performed. Median progression free survival (PFS) and overall survival (OS) were calculated as the time from start of niraparib treatment to subsequent radiologically confirmed relapse and death or last contact, respectively. The study included 304 patients with median age of 58 years (range 51-66). 260 (85%) enrolled patients were BRCA wild-type and 36 (11.9%) were BRCA mutated. At the time of diagnosis, most of patients (65.8%) underwent complete debulking surgery and were diagnosed with III-IV FIGO stage (78.8%). At the time of recurrence before niraparib maintenance 179 patients (58.9%) had received 2 previous lines of platinum-based chemotherapy and carboplatin in combination with PDL was the most frequent administered regimen (31.3%). Complete and partial radiological response to platinum-based CT was recorded in 44.4% and 27.0% of patients, respectively. Median PFS was 9.1 months (95% CI: 7.6-10.7) and median OS was 41.7 months (95% CI: 32.4-51.1). In a real-life setting, niraparib maintenance in patients with PSROC showed efficacy comparable with the published phase III data.

Real-world applications of PARPi maintenance therapy for recurrent ovarian cancer: A single-center study in China

ObjectiveTo assess the actual clinical application of poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) maintenance therapy in Chinese patients with recurrent ovarian cancer, and to explore prognostic factors associated with progression-free survival (PFS). MethodsWe retrospectively assessed real-world clinical data from our hospital using the inclusion and exclusion criteria of representative randomized controlled trials, analyzed the prognosis, and performed univariate and multivariate analyses of prognostic factors. ResultsBetween 2019 and 2022, the proportion of platinum-sensitive recurrence ovarian cancer patients who received PARPi maintenance therapy increased to 29.6%, 53.3%, 43.8% and 62.2%, respectively, each year. A total of 48 patients were included in the prognostic analysis, of which 32 and 16 received olaparib and niraparib, respectively. Using the criteria of the Study19 and SOLO2 studies, the olaparib group in our patients had coincidence rates of 56.3% and 18.8%, respectively. Using the criteria of the NOVA and NORA studies, the niraparib group had coincidence rates of 31.3% and 37.5%, respectively. Median PFS was 26.1 months (95% CI 20.2–32.1). Response to primary therapy was an independent prognostic factor for PFS (relative risk, 3.248; 95% CI 1.081–9.757, P = 0.036). ConclusionsPARPi maintenance therapy was also effective in real world applications. Complete response (CR) to primary therapy was an independent factor favorably affecting PFS. Therefore, primary treatment choices aimed at optimal cytoreduction during primary surgery and improving the CR rate should still be considered, which positively affects the long-term prognosis of patients in the new treatment mode.