Platinum-sensitive Recurrent Epithelial Ovarian Cancer Research Articles

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.

Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of secondary CRS and chemotherapy in comparison to chemotherapy alone for women with platinum-sensitive recurrent epithelial ovarian cancer.

57P Prognostic impact of functional domain of BRCA1/2 mutation in platinum-sensitive recurrent epithelial ovarian cancer patients receiving PARP inhibitors

57P Prognostic impact of functional domain of BRCA1/2 mutation in platinum-sensitive recurrent epithelial ovarian cancer patients receiving PARP inhibitors

Maintenance Chemotherapy in Patients with Platinum-Sensitive Relapsed Epithelial Ovarian Cancer after Second-Line Chemotherapy.

(1) Background: Our aim was to evaluate the efficacy and adverse effects of maintenance chemotherapy in platinum-sensitive recurrent epithelial ovarian cancer after second-line chemotherapy. (2) Methods: A total of 72 patients from a single institute who had been diagnosed with platinum-sensitive recurrent ovarian cancer and had experienced either complete or partial response after six cycles of second-line chemotherapy were divided into a standard group (n = 31) with six cycles or a maintenance group (n = 41) with more than six cycles. We then compared patient characteristics and survival outcomes between these two groups. (3) Results: In all patients, after primary management for the first recurrence, the maintenance group showed worse survival outcomes. Patients who had not undergone either surgery or radiotherapy were divided into complete response and partial response groups after six cycles of chemotherapy. In patients with partial response, maintenance chemotherapy led to a significant improvement in PFS (median, 3.6 vs. 6.7 months, p = 0.007), but no significant change in in OS. The median cycle number of maintenance chemotherapy was four. (4) Conclusions: Maintenance chemotherapy may still play an important role in patients with platinum-sensitive recurrent ovarian cancer, particularly in selected patient groups.

Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines.

Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.

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.

Timed adoptive T cell transfer during chemotherapy in patients with recurrent platinum-sensitive epithelial ovarian cancer

BackgroundThe presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that EOC may be sensitive to...

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.

Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer.

Triplet maintenance (olaparib, pembrolizumab, and bevacizumab) in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer: A multi-center, single-arm phase II study (OPEB-01).

5584 Background: The optimal treatment of BRCA 1/2 non-mutated patients with platinum-sensitive recurrent ovarian cancer remains unknown. In this study, we evaluated the efficacy and safety of triplet maintenance therapy in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer. Methods: BRCA 1/2 non-mutated patients with platinum-sensitive recurrent epithelial ovarian cancer, showing a complete/partial response after second-line platinum-based chemotherapy, were eligible. Triplet maintenance therapy (olaparib, bevacizumab, and pembrolizumab) was administered until disease progression or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS) rate at six months after therapy initiation. The secondary endpoints were PFS, overall survival, and safety. The translational objectives included biomarker evaluation with respect to survival outcomes. Results: Forty-four patients were enrolled (median age 61 years), majority with high-grade serous carcinoma (93.2%) and partial response (75.0%) to second-line chemotherapy. Overall, 54.6% were homologous recombination deficiency (HRD)-positive (genomic instability score ≥ 42) and 63.6% had PD-L1 positive tumors (combined positive score [CPS] ≥ 1). At 6 months, the PFS rate was 88.6% (95% confidence interval [CI] 75.4–96.2). The median PFS has not been reached. The most common ≥ grade 3 treatment-related adverse events (AEs) were anemia (20.5%) and neutropenia (6.8%), but there were no grade 4 AEs. Exploratory analysis demonstrated remarkable survival outcomes regardless of HRD status, whereas patients with PD-L1 CPS ≥ 1 showed improved PFS compared to those with PD-L1 CPS < 1 ( P = 0·032). Analysis of molecular consensus subtype of the pre-treatment tissue samples showed that patients with mesenchymal subtype demonstrated poor PFS, compared to non-mesenchymal subtypes (p = 0.0023). Conclusions: This is the first report on triplet maintenance therapy in BRCA non-mutated platinum-sensitive recurrent ovarian cancer. The results show that the triplet maintenance therapy is efficacious with manageable toxicity, showing a particular promise for patients with molecular consensus subtype other than mesenchymal. Clinical trial information: NCT04361370 .

Efficacy and toxicity of carboplatin and gemcitabine administered on day 1 and day 8 (day1&8) versus day 1-only for platinum-sensitive recurrent epithelial ovarian cancer

ObjectiveTo compare response rate, progression-free survival, overall survival, and toxicity of carboplatin and gemcitabine administered on day 1 and day 8 (day1&8) versus a modified day 1-only regimen in recurrent...

Role of minimally invasive secondary cytoreduction in patients with recurrent ovarian cancer

ObjectiveRetrospective series have shown minimally invasive secondary cytoreductive surgery is a feasible approach in selected cases of recurrent ovarian cancer. However, no predictors of minimally invasive secondary cytoreductive surgery feasibility...

A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for niraparib

Niraparib was approved for the treatment of platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube and primary peritoneal cancer. The authors retrospectively investigated niraparib-related adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Four algorithms were employed to quantify the signals of niraparib associated AEs, using data from the FAERS between 2017 and 2021. MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2019 and the GraphPad Prism 8 were used to conduct statistical analysis. There are 7,238,157 reports collected from the FAERS database, of which 11,701 reports listed niraparib as the ‘primary suspected (PS)’ drug. A total of 97 significant disproportionality PTs conforming to the four algorithms were simultaneously retained. Unexpected significant AEs such as neuropathy peripheral, photosensitivity reaction, gastrooesophageal reflux disease might also occur. The median onset time of niraparib-associated AEs was 18 days (interquartile range [IQR] 4–66 days), and most of the cases occurred within the first months after niraparib initiation. The study found niraparib-associated AEs and might provide important support for clinical monitoring and risk identification of niraparib.

Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study.

Epithelial Ovarian cancer (EOC) is the most lethal gynecologic cancer worldwide. Carboplatin (CP) is the main chemotherapeutic agent in the treatment of ovarian cancer. However, the development of a hypersensitivity reaction (HSR) in 10% to 15% of patients with EOC is an important limiting factor for the clinical use of CP. Herein, we aimed to investigate the efficacy and safety of CP-desensitization (CP-D) therapy in the treatment of recurrent patients with EOC. Forty-seven ovarian cancer cases treated with CP-desensitization at the Istanbul University Oncology Institute were retrospectively analyzed between 01.01.2017 and 01.01.2022. The decision for CP-D was based on the patients' history of HSR and/or a positive skin test. For all patients, a 6-hour 12-step rapid drug desensitization protocol with a 30-minutes premedication regimen was used. Forty-seven patients were included in this study, and the median age at diagnosis was 53 years (range; 27-80). Twenty-one (43.7%) patients had 1 or more comorbid diseases, and 12.7% had a previous history of drug allergy. On average, HSR due to carboplatin was identified after 9 (7-16) cycles, and carboplatin was administered n = 11 (range, 3-36) times to patients. The overall survival from the first desensitization procedure (0S2) was 42.2 months (range: 25.3-59.1), and the 1-, 2-, and 5-years survival rates were 92.6%, 75.6%, and 47.2%, respectively. The objective response rate (ORR) was 78.5%. Cumulatively, 496 CP-D procedures were performed, of which 478 (96.3%) were successfully completed. None of the patients included in this study developed severe (grade 3-4) HSR during CP administration (no adrenaline was used, no need for intensive care). No deaths due to CP-D were noted. CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR.

Hyperthermic Intraperitoneal Chemotherapy in the Management of Primary Epithelial Ovarian Cancer: A Debated Issue for Gynecologic Oncologists.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely investigated in patients with peritoneal carcinomatosis, including those with epithelial ovarian cancer (EOC), with conflicting results. The hyperthermia enhances drug tissue penetration, synergizes with several cytotoxic drugs including cisplatin, degrades BRCA2, suppresses homologous recombination, and elicits an anticancer immune response. A meta-analysis of retrospective studies including both patients with primary advanced EOC and those with recurrent platinum-sensitive EOC failed to detect a benefit in terms of progression-free survival (PFS) or overall survival (OS) from the addition of HIPEC after surgery. The aim of the present review was to analyze the recent randomized clinical trials designed to assess the value of HIPEC in the management of patients with primary advanced EOC. Although not free from criticism and bias, the available data from two phase III trials seem to suggest that the addition of HIPEC to interval debulking surgery after neoadjuvant chemotherapy significantly improves PFS and OS. Conversely, HIPEC does not appear to offer any advantage after primary debulking surgery. Several phase III trials are currently ongoing on these issues and the use of HIPEC is still a matter of debate in the scientific community. Additional translational research is strongly warranted to detect biological variables able to identify a subset of patients who may have a major benefit from this therapeutic approach. In particular, the clinical outcome of patients who undergo HIPEC should be correlated with BRCA status and homologous recombination repair status.

PICCOLO: An open-label, single arm, phase 2 study of mirvetuximab soravtansine in recurrent platinum sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression (300)

Objectives: Elevated FRα expression is a characteristic of epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising an FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has consistently shown clinically meaningful single-agent activity, along with favorable tolerability, in patients with high FRα expressing tumors (Moore ESMO 2019). Methods: PICCOLO is a single-arm, phase II study designed to evaluate the efficacy of mirvetuximab soravtansine in adult patients with recurrent platinum-sensitive EOC (including primary peritoneal cancer, or fallopian tube cancer) who would be, in the opinion of the investigator, candidates for a non-platinum, single-agent therapy for their next line of therapy. Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1CDx Assay (high expression; ≥ 75% of cells with PS2+ staining intensity) and two prior lines of platinum-based therapy are required for inclusion. Patients with a documented platinum allergy require only one prior line of platinum. PICCOLO will enroll 75 patients who will receive intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle. The primary efficacy endpoint is objective response rate (ORR; by investigator) and secondary endpoints include duration of response, progression-free survival, overall survival, CA-125 response, and safety and tolerability. PICCOLO is a global study that opened for enrollment in August 2021. Clinical trial information: NCT05041257. Objectives: Elevated FRα expression is a characteristic of epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising an FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has consistently shown clinically meaningful single-agent activity, along with favorable tolerability, in patients with high FRα expressing tumors (Moore ESMO 2019). Methods: PICCOLO is a single-arm, phase II study designed to evaluate the efficacy of mirvetuximab soravtansine in adult patients with recurrent platinum-sensitive EOC (including primary peritoneal cancer, or fallopian tube cancer) who would be, in the opinion of the investigator, candidates for a non-platinum, single-agent therapy for their next line of therapy. Confirmation of high FRα positivity by immunohistochemistry using the Ventana FOLR1CDx Assay (high expression; ≥ 75% of cells with PS2+ staining intensity) and two prior lines of platinum-based therapy are required for inclusion. Patients with a documented platinum allergy require only one prior line of platinum. PICCOLO will enroll 75 patients who will receive intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle. The primary efficacy endpoint is objective response rate (ORR; by investigator) and secondary endpoints include duration of response, progression-free survival, overall survival, CA-125 response, and safety and tolerability. PICCOLO is a global study that opened for enrollment in August 2021. Clinical trial information: NCT05041257.

Effectiveness of Platinum-Based Chemotherapy after Progression on Poly ADP Ribose Polymerase (PARP) Inhibitor in Epithelial Ovarian Cancer (042)

<b>Objectives:</b> PARP inhibitors have revolutionized ovarian cancer care with dramatic improvements in progression-free (PFS) and overall survival when used as maintenance therapy following platinum-based treatment. However, much remains unknown about the response to subsequent treatment after progression on PARP inhibitor (PARPi) therapy, including whether a 6-month platinum-free interval is an appropriate benchmark for using a platinum-based regimen. Therefore, we aimed to assess response to platinum-based chemotherapy in women with platinum-sensitive recurrent epithelial ovarian cancer (EOC) after progression on PARPi. <b>Methods:</b> We performed a retrospective chart review of all cases of EOC prescribed a PARPi at a tertiary care center from 2015 to 2020. We included patients who progressed on PARPi and were subsequently treated with platinum-based chemotherapy. Patients who received fewer than six months of PARPi treatment were excluded. The primary outcome was PFS on the platinum regimen (ptPFS), defined as the time from the start of platinum therapy to physician documented progression. Germline and somatic <i>BRCA</i> testing, number of prior lines of chemotherapy, duration of therapy with PARPi and subsequent platinum regimen, and demographic data were collected for each case. An accelerated failure time model was developed to assess the primary outcome with a multivariable model including <i>BRCA</i> status, prior lines of chemotherapy, and time on PARPi in 6-month intervals. <b>Results:</b> A total of 283 charts were reviewed, and 40 cases met the inclusion criteria. Of these, 60% (<i>n</i>=24) had a <i>BRCA</i> mutation (<i>BRCA</i>mut); 75% (<i>n</i>=18) were germline and 25% (<i>n</i>=6) were somatic mutations. Twenty percent (<i>n</i>=8) of patients received a PARPi after first-line treatment, 45% (<i>n</i>=18) after second, 28% (<i>n</i>=11) after third, and 7% (<i>n</i>=3) after fourth. Sixty percent (<i>n</i>=24) of patients were prescribed olaparib, 20% (<i>n</i>=8) niraparib, 10% (<i>n</i>=4) rucaparib, and 10% received two agents due to toxicity with their first. The median time on PARPi was 411 days, and the median ptPFS was 218 days. In the multivariable model (Table 1), <i>BRCA</i> mutations were associated with decreased ptPFS (<i>BRCA</i>wt 274 days vs <i>BRCA</i>mut 170 days, p=0.004). The median time on PARPi greater than 18 months was associated with improved ptPFS compared to 12-18 months and <12 months (262 vs 188 vs 163 days, respectively, p=0.007). The number of prior lines of therapy was not associated with ptPFS (p=0.13). <b>Conclusions:</b> This retrospective analysis supports the ongoing use of platinum-based chemotherapy in recurrent EOC after progression on PARPi therapy with outcomes comparable to those seen in OCEANS and GOG-213. These data suggest that resistance to PARPi does not necessarily imply platinum resistance. Poorer ptPFS in tumors with a <i>BRCA</i>mut compared to those without was unexpected. While the data surrounding post PARPi treatment response is limited, growing evidence from the recently reported OReO trial corroborates this finding. This raises the question of a difference in the underlying mechanism leading to platinum resistance and PARPi resistance in <i>BRCA</i>mut versus <i>BRCA</i>wt EOC. Molecular assessment of recurrent tumors with clinical correlation will be important to optimize treatment approaches.

Efficacy and toxicity of carboplatin and gemcitabine dosed on day 1/day 8 versus day 1 alone for platinum-sensitive recurrent epithelial ovarian cancer.

5541 Background: Carboplatin, gemcitabine +/- bevacizumab is a preferred regimen for recurrent, platinum-sensitive ovarian cancer (PSOC). A phase III trial established that the regimen of carboplatin on Day 1 (D1) and gemcitabine on D1 and Day 8 (D8) was associated with acceptable toxicity and improved progression free survival (PFS) compared to carboplatin alone. Treatment with gemcitabine on D8 incurs more exposure to cytotoxic therapy and increased burden on patients and the healthcare system, especially during the COVID-19 pandemic. However, it is unknown whether D1/D8 gemcitabine imparts an improvement in efficacy compared to D1 alone. Our objective was to compare efficacy and toxicity of carboplatin and gemcitabine D1/D8 (CG-D1/8) with a modified D1 regimen (CG-D1). Methods: A retrospective single-institution cohort study was performed in women with recurrent PSOC treated with carboplatin, gemcitabine +/- bevacizumab from 2009-2020. Data was analyzed by intention to treat comparing women who received CG-D1/8 vs CG-D1. Data was also analyzed by 3 groups: CG-D1/8 vs CG-D1/8 but dropped D8 vs CG-D1. The primary endpoint was response rate (RR), defined as complete or partial response at 6 cycles or maximum cycles if &lt;6. Secondary outcomes included PFS, overall survival (OS), toxicity, Neulasta use and dose reduction. Results: Of 200 patients, 26% completed CG-D1/D8, 21.5% started CG-D1/D8 but dropped D8, and 52.5% received CG-D1. There were no significant differences in age, race, or ECOG between cohorts. Among CG-D1/D8, 45.3% dropped D8 primarily due to neutropenia (51.2%) or thrombocytopenia (30.2%). The RR at 6 cycles was 68.7% for CG-D1/8 completed, 70.7% for CG-D1/8 dropped D8, and 69.3% for CG-D1 (p=0.97). The median PFS was 13.1, 12.1 and 12.4 months for CG-D1/8 completed, CG-D1/8 dropped D8, and CG-D1, respectively (p=0.29). Similarly, median OS was 28.2, 33.5 and 34.3 months for the above groups respectively (p=0.42). While there was no difference in concurrent bevacizumab use for CG-D1/8 and CG-D1 (34.7% vs 29.5%, p=0.43), among the CG-D1/8 patients, a significantly higher proportion of patients who dropped D8 received bevacizumab (51.2% vs 21.2%, p=0.006). Table 1 lists secondary outcomes. Conclusions: There was no significant difference in RR, PFS or OS among women with PSOC receiving CG-D1/8 vs CG-D1, regardless of whether D8 was dropped. CG-D1/8 was associated with significantly greater hematologic toxicity. These findings suggest a modified D1 regimen may be a suitable alternative to standard CG-D1/8 treatment and warrant prospective validation. [Table: see text]

A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in patients with platinum-sensitive, recurrent ovarian cancer previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial.

TPS5610 Background: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi. Methods: The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate and 4 of planned 44 patients have been enrolled. Clinical trial information: NCT04734665.

The impact of secondary cytoreductive surgery in platinum sensitive recurrent ovarian cancer treated with upfront neoadjuvant chemotherapy and interval debulking surgery

ObjectiveThe aims of the present study were to assess the oncological outcomes of platinum-sensitive recurrent ovarian cancer patients undergoing secondary cytoreduction (SCS) after treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) at diagnosis and to compare the performance of different selection models in these patients. MethodsRetrospective, observational, single-center cohort study including patients with platinum-sensitive recurrent epithelial ovarian cancer with abdominal/inguinal/cardiophrenic disease between November 2012 and November 2020. Patients were selected as surgical candidates with PET/CT-scan and with diagnostic laparoscopy. Results272 patients were included in the study. Of these, 165 (60.7%) patients were treated with PDS at diagnosis and 107 (39.3%) with IDS. SCS was performed in 178 (65.4%) cases, with complete gross resection achieved in 155/178 (87.1%). No progression-free survival (PFS) difference was demonstrated when patients treated with PDS were compared with those treated with NACT+IDS at first diagnosis (median 21 versus 21 months; p = 0.684); no post-recurrence survival (PRS) difference was evident between the two groups (median 81 versus 77 months, respectively; p = 0.574). Current selection models to candidate patients to SCS adequately performed in patients treated with IDS at diagnosis, as well as in the PDS group, with combination of PET/CT-scan and laparoscopy being an accurate tool in prediction of no gross residual disease at SCS in this pre-selected population. ConclusionsPatients with platinum-sensitive recurrent epithelial ovarian cancer treated with NACT/IDS as primary treatment have similar post-recurrence survival outcomes of those treated with PDS. Current models to select patients for SCS can be safely applied to IDS patients.

Response to Chemotherapy and Clinical Outcome of Patients With Recurrent Epithelial Ovarian Cancer After PARP Inhibitor Maintenance Treatment: A Multicenter Retrospective Italian Study.

To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi. This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum-based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum-free interval (PFI). Of the 28 patients with PFI <6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum-based chemotherapy,11; trabectedin + PLD, 10; non platinum-single agent, 21). Thirty-one of the 32 patients with PFI >12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum - single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI <6 months, 6-12 months, and >12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively. Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.