Platinum-sensitive Recurrent Ovarian Cancer Patients Research Articles

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.

Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): final overall survival analysis of a phase 3 randomised, placebo-controlled trial

Niraparib significantly prolonged progression-free survival versus placebo in patients with platinum-sensitive, recurrent ovarian cancer (PSROC), regardless of germline BRCA mutation (gBRCAm) status, in NORA. This analysis reports final data on overall survival (OS). This randomised, double-blind, placebo-controlled, phase 3 trial enrolled patients across 30 centres in China between 26 September 2017 and 2 February 2019 (clinicaltrials.gov, NCT03705156). Eligible patients had histologically confirmed, recurrent, (predominantly) high-grade serous epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma (no histological restrictions for those with gBRCAm) and had received ≥2 prior lines of platinum-based chemotherapy. Patients were randomised (2:1) to receive niraparib or placebo, with stratification by gBRCAm status, time to recurrence following penultimate platinum-based chemotherapy, and response to last platinum-based chemotherapy. Following a protocol amendment, the starting dose was individualised: 200mg/day for patients with bodyweight <77kg and/or platelet count <150×103/μL at baseline and 300mg/day otherwise. OS was a secondary endpoint. Totally, 265 patients were randomised to receive niraparib (n=177) or placebo (n=88), and 249 (94.0%) received an individualised starting dose. As of 14 August 2023, median follow-up for OS was 57.9 months (IQR, 54.8-61.6). Median OS (95% CI) with niraparib versus placebo was 51.5 (41.4-58.9) versus 47.6 (33.3-not evaluable [NE]) months, with hazard ratio [HR] of 0.86 (95% CI, 0.60-1.23), in the overall population; 56.0 (36.1-NE) versus 47.6 (31.6-NE) months, with HR of 0.86 (95% CI, 0.46-1.58), in patients with gBRCAm; and 46.5 (41.0-NE) versus 46.9 (31.8-NE) months, with HR of 0.87 (95% CI, 0.56-1.35), in those without. No new safety signals were identified, and myelodysplastic syndromes/acute myeloid leukaemia occurred in three (1.7%) niraparib-treated patients. Niraparib maintenance therapy with an individualised starting dose demonstrated a favourable OS trend versus placebo in PSROC patients, regardless of gBRCAm status. Zai Lab (Shanghai) Co., Ltd; National Major Scientific and Technological Special Project for "Significant New Drugs Development" in 2018, China [grant number 2018ZX09736019].

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.

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.

Cost-effectiveness analysis of niraparib maintenance therapy in Chinese patients with platinum-sensitive recurrent ovarian cancer

ObjectivesThis study aimed to evaluate the cost-effectiveness of niraparib versus routine surveillance as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer in China. MethodA three-state partitioned survival model that adopted a lifetime horizon with a 4-week cycle length was developed. Efficacy data were derived from the NORA study. Cost and utility data were obtained from published studies and online databases. The cost and health outcomes were discounted at an annual rate of 5%. In this analysis, the primary outcomes included quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) thresholds were set at 1 to 3 times the gross domestic product per capita of China in 2022 ($12,741 to $38,233/QALY). Sensitivity analyses were conducted to verify the robustness of the model results. ResultsIn the base-case analysis, niraparib was not found to be cost-effective, with an ICER of $42,888/QALY compared with routine surveillance at the WTP thresholds. One-way deterministic sensitivity analyses indicated that the ICER value was most sensitive to the cost of subsequent treatment in placebo group. The probabilistic sensitivity analysis suggested that at the WTP thresholds, the probability of niraparib being cost-effective was 2.9% to 50.1%. ConclusionsNiraparib improves the survival benefit of platinum-sensitive recurrent ovarian cancer patients. However, it seems to be less cost-effective, as it has higher costs than routine surveillance at the WTP thresholds. Reasonable dose reduction according to the patient's actual situation or lowering the price of niraparib can improve its cost-effectiveness.

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...

Role of HIPEC after Complete Cytoreductive Surgery (CRS) in Peritoneal Recurrence of Platinum-Sensitive Recurrent Ovarian Cancer (OC): The Aim for Standardization at Two Reference Centers for CRS.

This bicentric study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for platinum-sensitive recurrent ovarian cancer patients. The data of 88 patients with the first peritoneal recurrence of platinum-sensitive epithelial ovarian cancer who underwent CRS and HIPEC from a prospective HIPEC registry were retrospectively investigated. Endpoints were feasibility, chemotherapeutic compound, time of exposure, complications, and overall survival. The median follow-up was 4.7 years (95%-CI 4.6-5.5). The median age was 55.8 years (IQR: 50.3-66.2). Eighty-four patients (95.5%) had high-grade serous histology. The median peritoneal cancer index was 12.0 (IQR: 7.0-20.5). Sixty-five patients (73.9%) had complete cytoreduction (CCR 0). Thirty-eight patients (43.2%) received HIPEC for 60 min, and fifty patients (56.8%) for 90 min. Eighteen patients (20.5%) had grade III to IV complications. One patient (1.1%) died perioperatively. The overall median survival was 43.1 months (95%-CI 34.1-52.2), and the 5-year survival rate was 39.7%. Only 90 min HIPEC and cisplatin were associated with survival. In well-selected patients with platinum-sensitive recurrent ovarian cancer, survival may correlate with complete CRS and 90 min cisplatin-based HIPEC. We confirmed the results of primary OC studies; therefore, this combination should be used for further analysis in the recurrent situation.

Simplified Selection Criteria for Secondary Cytoreductive Surgery in Recurrent Ovarian Cancer.

Simple SummaryEligibility for secondary cytoreductive surgery (SCS) in ovarian cancer is dependent on multiple confounding factors. In this study, we evaluated the clinical characteristics of 262 patients with recurrent ovarian cancer to assess the impact of SCS on patient survival and establish simplified criteria for the selection of patients who would most likely be benefitted from SCS. We observed that the median survival was significantly longer in the patients who received SCS compared with those who received chemotherapy alone. As for the indication of the surgery, limited regional recurrence (single region or up to three regions with limited carcinomatosis) emerged as the simplified factor that could predict no residual disease after SCS.(1) Background: Multiple confounding factors influence the indications for secondary cytoreductive surgery (SCS) in patients with ovarian cancer (OC). We aimed to identify the factors associated with patients most likely to benefit from SCS. (2) Methods: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer from 2003 to 2021. The potential factors influencing treatment outcomes and survival between patients who received chemotherapy alone and those who received SCS after recurrence were evaluated. (3) Results: Recurrent OC was identified in 262 patients, with a median age of 53 (20–80) years. Of these patients, 87.4% had an initial stage III/IV disease. Eighty-nine (34%) patients received SCS. The median survival was 41.0 (95% confidence interval [CI], 37.4–44.5) months and 88.0 (95% CI, 64.2–111.7) months in the chemotherapy and surgery groups, respectively. A multivariate analysis showed limited regional carcinomatosis (single region or up to three regions with limited carcinomatosis) (p = 0.045) as the only significant factor for predicting no residual disease after SCS. In platinum-sensitive recurrent patients with limited regional recurrence, the complete resection rate was 87.6%. (4) Conclusions: SCS had a significant impact on survival in the selected patient population. Limited regional recurrence (single region or up to three regions with limited carcinomatosis) may be a simple criterion for SCS in platinum-sensitive recurrent OC patients.

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.

Survival in recurrent ovarian cancer patients before and after the bevacizumab era: an observational single-centre study

A retrospective observational study was carried out in Baskent University School of Medicine, Ankara, Turkey. Recurrent ovarian cancer patients treated between 2007 and 2017 were divided into two groups according to their bevacizumab status. The primary endpoints were overall survival (OS) and safety. Three hundred and ninety-six patients enrolled in this study, 200 (50.5%) received bevacizumab while 196 (49.5%) patients never received bevacizumab. The median follow-up time was 48.2 and 47.6 months, respectively. The 5-year OS was 61% and 46%, respectively (p=.007). In multivariate analysis, only platinum-sensitivity (HR: 3.75, 95% CI: 3.0–5.32; p<.001) was identified as independent prognostic factors. In subgroup analyses according to platinum status, bevacizumab did not affect the 5 year OS in platinum sensitive patients (64% versus 68% p=.28) but increased survival in platinum resistant patients (36% versus 44%, p=.00). The rate of grade III–IV haematologic toxicities was 13.7% in the bevacizumab group and 11% in the other group (p=.6). Impact Statement What is already known on this subject? Bevacizumab increases the progression-free survival in platinum-sensitive and resistant recurrent ovarian cancer patients without changing overall survival. What do the results of this study add? Bevacizumab did not affect OS in platinum sensitive recurrent ovarian cancer patients however improved OS in platinum resistant patients with mild toxicity. What are the implications of these findings for clinical practice and/or further research ? This study emphasised the crucial role of bevacizumab in the treatment of recurrent ovarian cancer patients.

Real-world treatment patterns and outcomes in platinum-sensitive recurrent high-grade serous ovarian cancer patients.

Aim: To describe the overall cancer-related healthcare utilization patterns, treatment patterns and outcomes in women diagnosed with platinum-sensitive recurrent high-grade serous ovarian cancer. Patients & methods: Subanalysis of the Spanish sample of a retrospective, noninterventional, multinational, observational study. Results:BRCA-mutated patients had better outcomes in terms of progression-free survival and overall survival than patients who were BRCA wild-type. It was observed that patients' treatment outcomes after the first recurrence progressively worsened as the patient underwent subsequent chemotherapy lines. Healthcare resource utilization when accounting for the follow-up time did not substantially differ between BRCA1/2-mutated and BRCA wild-type patients. Conclusion:BRCA1/2 mutation carriers have better treatment outcomes, including longer survival, without a negative impact on the use of healthcare resources.

Secondary Cytoreductive Surgery in Platinum Sensitive Recurrent Ovarian Cancer: A Meta-Analysis

Background: The survival impact of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer patients was studied. Methods: Published studies from 1983 to 2020 that were in accordance with our inclusion criteria from MEDLINE, EMBASE, and Cochrane library were identified. To integrate the effect size of single-arm studies, meta-analysis was performed using death rate as a primary outcome. The effect of complete cytoreduction and optimal cytoreduction on survival was evaluated using meta-regression. The pooled death rate was presented with a 95% confidence interval (CI). The publication bias was evaluated with the funnel plot and egger’s test, and sensitivity analysis were performed. To overcome missing death rates, the linear regression model was performed on log-transformed median overall survival time using the study size as a weight. Findings: Of the 75 eligible studies that satisfied the inclusion criteria, 33 studies that reported death rates with 2,261 patients were used for meta-analysis. Following a heterogeneity test, we considered a random effect model because the p-value of Cochrane Q test was less than 0·001, and Higgins’s I 2 statistics was 91%, indicating considerable heterogeneity. The pooled death rate was 0·440 (95% CI, 0·374-0·505), and both the complete and optimal cytoreductions were associated with better survival outcomes as significant moderators in the meta-regression model (p <0·001 and p=0·010, respectively). Although fourteen studies were located outside the funnel plot, sensitivity analysis showed similar results, and egger’s test also showed no significant publication bias (p=0·733). In the linear regression model based on 55 studies reporting median overall survival time, median overall survival time increases by 8·619% and 6·531% when the proportion of complete and optimal cytoreduction increases by 10% after adjusting other variables. Interpretation: Secondary cytoreductive surgery without postoperative residual disease in more recent publications is associated with increased overall survival in platinum-sensitive recurrent ovarian cancer. Funding: The study was funded by the National Cancer Centre, Korea (NCC2110790). Declaration of Interest: All other authors declare no competing interests.

Abstract A05: Maintenance therapy for platinum-sensitive (PS) recurrent ovarian cancer (rOC): What are we actually choosing?

Abstract Background: Treatment for platinum-sensitive (PS) recurrent ovarian cancer (rOC) patients generally consists of retreatment with platinum-based chemotherapy. Maintenance therapy with a targeted agent can extend the interval before progression. Patients with a somatic or germline BRCA mutation (BRCAm) have a greater clinical benefit with maintenance PARPi compared to BRCA wild-type (BRCAwt). Data have shown that ~50% of patients eligible for maintenance therapy do not receive it and variation in the type of maintenance therapy prescribed (BEV vs. PARPi) exists both nationally and within institutions. The objective of this study was to analyze the utilization of maintenance therapy in PS rOC at a large, high-volume academic institution. Methods: This retrospective cohort study evaluated PS rOC patients seen at the University of Alabama at Birmingham (UAB) who completed 2nd line or greater platinum-based chemotherapy for 3-8 cycles since March 27, 2017 (date of FDA approval for PARPi maintenance). Medical records on all patients were reviewed from 9/2018-2/2019 to capture a recent representative sample. Percent of patients and what type of maintenance therapy they received after platinum-based treatment were assessed. The difference in BRCA status between these groups was evaluated. Progression-free survival (PFS) was compared between those who received maintenance therapy and those that did not. PFS was defined as the date of initiation of platinum-based chemotherapy until progression of disease or death regardless of whether or not they were on maintenance therapy (based on PFS definition in BEV maintenance phase III clinical trials). Results: There were 61 PS rOC patients seen during this time period who were eligible for maintenance therapy. 72% received maintenance therapy: 86% (n=38) received PARPi and 14% (n=6) received BEV. PFS following platinum-based chemotherapy with at least one dose of maintenance therapy was 13.4m (6.5-23.6) vs. 11.4m (7.5-27.0) with no maintenance therapy. Germline and somatic BRCA status were known in ~75% of the cases. 60% (9/15) of the patients with a BRCAm (somatic or germline) received maintenance therapy; all patients received a PARPi. PFS in these patients was 17.5m (15.6-19.0) vs. 10.7m (8.0-27.0) with no maintenance therapy. Conclusions: Consistent with randomized control trials, maintenance therapy prolonged PFS in PS rOC patients, which was more pronounced in BRCAm patients who received a PARPi, although not statistically significant in our small cohort of patients. At our institution, &amp;gt;50% of patients who were eligible for maintenance therapy received it, which is higher than data obtained from national databases. While 30% of the patients did not receive maintenance therapy, this could have been based on a multitude of factors including toxicity, degree of benefit, cost, etc. Only 60% of the patients with known BRCAm received maintenance PARPi, which warrants further investigation into the potential barriers that exist. Citation Format: Hannah Beer, Jaclyn Arquiette, Angelina I. Londono, Mckenzie Foxall, Charles A. Leath III, Rebecca C. Arend. Maintenance therapy for platinum-sensitive (PS) recurrent ovarian cancer (rOC): What are we actually choosing? [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A05.

The value of secondary neoadjuvant chemotherapy in platinum-sensitive recurrent ovarian cancer: a case-control study post GOG-0213 trial

BackgroundThe prognostic value and optimal resection outcome related factors of the secondary cytoreduction surgery (SCR) in Platinum-sensitive recurrent ovarian cancer (PSOC) patients were still in doubt. The present retrospective study aims to determine the relationship between the objective response of secondary neo-adjuvant chemotherapy (SNAC) and the resection outcome of SCR.MethodsData were reviewed from 142 type II PSOCs who underwent SCR in Jiangsu Institute of Cancer Research between 1996 and 2016. Among them, 55 cases received preliminary Platinum based SNAC before SCR. Logistic regression analysis was used to explore optimal SCR related factors. Cox proportional hazards model and log-rank test were used to assess the associations between the survival durations and covariates.ResultsOptimal initial CRS (p = 0.02), disappearance of ascites after SNAC (p = 0.04) recurrent status (p = 0.02) and longer Platinum-free interval (p = 0.01) were the independent indicators of optimal SCR. Optimal SCR was associated with time to progression (TTP) but not overall survival (OS) (p = 0.04 and p = 0.41). The TTP and OS of PSOCs underwent SNAC were similar to those patients underwent SCR (p = 0.71, and p = 0.77, respectively) directly.ConclusionsSNAC might be another choice for PSOCs were not suitable for directly SCR. Optimal SCR had survival benefit in PSOCs whenever underwent SNAC or not.

Secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer before olaparib maintenance: Still getting any benefit? A case-control study

ObjectiveThe role of secondary cytoreductive surgery (SCS) in platinum-sensitive recurrent ovarian cancer (PSROC) is still controversial. We investigated the role of SCS in PSROC patients with BRCA1/2 mutation (BRCAmut) who received platinum-based chemotherapy followed by olaparib maintenance. MethodsThis is a case-control study. Patients with first PSROC admitted to our Gynecologic Oncology Unit between 2014 and 2018 were identified. Main eligibility criteria: positive BRCA1/2 germline or somatic mutation status and olaparib maintenance at primary recurrence after response to platinum-based chemotherapy. Cases were those who received SCS followed by medical treatment (SCS-CT-OLA, group 1), controls were those who received medical treatment alone (CT-OLA, group 2). ResultsOverall, 46 patients were identified; 23 (50%) BRCAmut women undergoing SCS followed by platinum-based chemotherapy and olaparib maintenance were matched with 23 (50%) BRCAmut women who only received medical treatment. Groups were well balanced: no statistical differences were found with regard of age, mutational status, treatment’s approach at diagnosis, timing and patterns of disease presentation at recurrence. Median time to first subsequent therapy (TFST) was significantly longer in the SCS-CT-OLA than in the CT-OLA group (42 months vs 16 months; p = 0.05). Also, SCS-CT-OLA patients had the best post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS-CT-OLA group versus 42% in CT-OLA group (p = 0.02). ConclusionsSCS increases TFST and PRS in PSROC patients with BRCAmut candidate for olaparib maintenance after platinum-based chemotherapy. Prospective studies are needed. In the era of personalized medicine, indication to SCS should be individualized.

Cost-Effectiveness of Niraparib and Olaparib as Maintenance Therapy for Patients with Platinum-Sensitive Recurrent Ovarian Cancer.

The recent approval of olaparib and niraparib as maintenance therapy can significantly affect the management of ovarian cancer. Clinical benefits, however, come with trade-offs in adverse events and costs. To evaluate the cost-effectiveness of new ovarian cancer poly-ADP ribose polymerase (PARP) inhibitor therapies, olaparib and niraparib, as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer. A decision tree model was constructed to evaluate the costs and effectiveness of olaparib and niraparib compared with placebo from a U.S. health care sector perspective. Costs included drug costs and costs of disease monitoring and management of adverse events throughout the treatment course. Costs were estimated from RED BOOK, Medicare reimbursement rates, and the literature and reported in 2017 U.S. dollars. Clinical effectiveness was measured in progression-free survival (PFS) life-years based on clinical trial results (NCT00753545, NCT01874353, and NCT01847274). The incremental cost-effectiveness ratio (ICER) was computed by dividing the incremental cost by the incremental effectiveness. At base case, niraparib was the more effective treatment option with slightly higher PFS, followed by olaparib. The ICERs for niraparib and olaparib compared with common baseline placebo were $235K and $287K per PFS life-year, respectively, with olaparib extended-dominated by niraparib. Both drugs were associated with lower ICERs in patients with a gBRCA mutation than in patients without a gBRCA mutation. One-way sensitivity analysis suggested that drug prices and PFS could affect ICERs significantly, but the ICERs remained above $100K per PFS life-year within the plausible ranges of all parameters. Probabilistic sensitivity analysis suggested that niraparib was associated with higher net benefits compared with placebo only when willingness-to-pay (WTP) values were above $210K per PFS life-year thresholds. PARP inhibitors niraparib and olaparib will extend PFS in platinum-sensitive recurrent ovarian cancer patients but are also associated with high drug acquisition costs. The base case ICERs were around or above $250K per PFS life-year in this model. No formal cost-effectiveness WTP threshold for health technology assessment exists in the United States. At a reference WTP of $100K per PFS life-year, the PARP inhibitors may not be cost-effective options. This study was unfunded. The authors have nothing to disclose.

Non-pegylated liposomal doxorubicin (NPLD, Myocet®) + carboplatin in patients with platinum sensitive ovarian cancers: A ARCAGY-GINECO phase IB-II trial

BackgroundCarboplatin and pegylated liposomal doxorubicin combination is a standard regimen in platinum-sensitive recurrent ovarian cancer patients. The pegylated liposomal doxorubicin shortage from 2011 to 2013 urged assessment of the efficacy and tolerance of non-pegylated liposomal doxorubicin in combination with carboplatin. MethodsMYCA was a multicenter 2-step phase Ib-II single arm trial meant to assess the safety and efficacy of carboplatin AUC 5 mg/min.mL combined with non-pegylated liposomal (dose escalation from 40 to 50 mg/m2 during phase Ib step; and 50 mg/m2 during phase II step), every 4 weeks in patients with platinum-sensitive relapse. The primary objective was disease control rate (DCR) at 12 months. ResultsFrom 2012 to 2014, 87 patients were enrolled. They were treated as second (78%) or third line (22%) treatment. Total of 67 patients (78%) completed 6 cycles. G-CSF support was prescribed to 58% patients. The DCR at 12 months was 30.0% (95% CI, 20.3–39.7); the median PFS was 10.0 months (95% CI, 8.6–11.0). The median overall survival was 28.1 months (95% CI, 22.3–32.5); and the objective response rate was 58% (95% CI, 47–68). Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 17%, 13% and 1%, respectively; febrile neutropenia in 6%. One patient who did not receive GCSF support died from febrile neutropenia. ConclusionNon-pegylated liposomal doxorubicin-carboplatin combination exhibits an acceptable safety profile, with GCSF prophylaxis. Acknowledging the lack of direct comparison, efficacy in terms of 12 month DCR was comparable with standard treatments.

P1.12-04 A Ph3 Study of Niraparib as Maintenance Therapy in 1L Platinum Responsive Extensive Disease Small Cell Lung Cancer Patients

Small cell lung cancer (SCLC) accounts for 15% of lung cancer, characterized by early dissemination and rapid development of chemo-resistant disease after platinum response (60-80%). Less than 2% of extensive disease SCLC (ED-SCLC) patients survive 5 years. The bi-allelic loss or inactivation of TP53 and RB1 is common in SCLC, the poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA damage repair enzyme, is highly expressed in SCLC, and SCLC is sensitive to platinum based chemotherapy, suggesting that the defect in DNA damage repair pathways plays an important role in SCLC. ZL2306/ Niraparib is a highly selective PARP-1/2 inhibitor which was exclusively licensed for development in China by Zai Laboratory from TESARO. In SCLC PDX model, niraparib demonstrated anti-tumor activities as monotherapy. In addition, niraparib demonstrated promising tumor growth inhibition in maintenance post platinum treatment in platinum sensitive SCLC PDX models. Clinically, in phase III NOVA study, niraparib demonstrated clear clinical benefit as maintenance treatment by significantly extending progression free survival in all platinum-sensitive recurrent ovarian cancer patients regardless gBRCA or HRD status which led to the approval by FDA and EMA in ovarian cancer. It is suggested that niraparib maintenance therapy could provide potential clinical benefit in platinum responsive SCLC. ZL-2306-005 is a randomized double-blind multi-center phase 3 study to evaluate the efficacy and safety of niraparib versus placebo as maintenance therapy in ED-SCLC patients who have had responses to platinum based chemotherapy. Approximately 590 Chinese patients with histologically or cytologically confirmed ED-SCLC who have achieved either complete response or partial response to their platinum based chemotherapy to their newly diagnosed disease will be randomized (2:1) to 2 groups, receiving either ZL-2306 or placebo in ZL-2306-005 study. Patients need to complete 4 cycles of etoposide + cisplatin/ carboplatin. All patients will be stratified by gender, LDH level and history of prophylactic cranial irradiation. ZL-2306 will be started with 300mg PO QD for patients with a baseline body weight ≥77 kg and a baseline platelet count ≥150,000/μL, or 200 mg PO QD for patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL based on RADAR analysis in NOVA study. Patients will remain on treatment until disease progression or intolerable toxicity. The co-primary endpoints are PFS assessed by independent central radiologic review and OS; the secondary endpoints are PFS assessed by investigator, CFI, QoL, safety and tolerability. Section not applicable Section not applicable