Niraparib Maintenance Research Articles

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...

AGO-OVAR 28/ENGOT-ov57. Niraparib alone versus niraparib in combination with bevacizumab in patients with carboplatin-taxane-based chemotherapy in advanced ovarian cancer: a multicenter randomized phase III trial

BackgroundPhase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian...

789P Real-world (RW) duration of treatment in first-line maintenance (1Lm) niraparib monotherapy in epithelial ovarian cancer (EOC): CHAR1ZMA study

789P Real-world (RW) duration of treatment in first-line maintenance (1Lm) niraparib monotherapy in epithelial ovarian cancer (EOC): CHAR1ZMA study

LBA37 Atezolizumab (atezo) combined with platinum-based chemotherapy (CT) and maintenance niraparib for recurrent ovarian cancer (rOC) with a platinum-free interval (TFIp) >6 months: Primary analysis of the double-blind placebo (pbo)-controlled ENGOT-Ov41/GEICO 69-O/ANITA phase III trial

LBA37 Atezolizumab (atezo) combined with platinum-based chemotherapy (CT) and maintenance niraparib for recurrent ovarian cancer (rOC) with a platinum-free interval (TFIp) >6 months: Primary analysis of the double-blind placebo (pbo)-controlled ENGOT-Ov41/GEICO 69-O/ANITA phase III trial

Efficacy and safety of olaparib, olaparib plus bevacizumab and niraparib maintenance treatment in Japanese patients with platinum-sensitive advanced ovarian cancer.

To investigate whether maintenance treatment could be safely and effectively performed with olaparib, olaparib plus bevacizumab and niraparib in platinum-sensitive advanced ovarian cancer at multiple institutions in Japan. We investigated progression-free survival and adverse events in 117 patients with platinum-sensitive advanced ovarian cancer treated with maintenance therapy. The median progression-free survival of 117 patients was 20.1months. Patients with germline BRCA pathogenic variants had a significantly better prognosis than the other groups (P<0.001). Furthermore, in the multivariate analysis, stage IV (P=0.016) and germline BRCA wild-type (P≤0.001) were significantly associated with worse progression-free survival in patients with advanced ovarian cancer. Regarding adverse events, all three types of maintenance treatment were significantly worse than chemotherapy given before maintenance treatment with respect to renal function (olaparib, P=0.037; olaparib plus bevacizumab, P<0.001; and niraparib, P=0.016). Maintenance treatment was performed effectively and safely. Renal function deterioration is likely to occur during maintenance treatment, and careful administration is important in platinum-sensitive advanced ovarian cancer.

Impact of dose modifications due to treatment-emergent adverse events (TEAEs) on the efficacy of niraparib maintenance treatment with an individualized starting dose in patients (Pts) with newly diagnosed advanced ovarian cancer (aOC) (1266)

Impact of dose modifications due to treatment-emergent adverse events (TEAEs) on the efficacy of niraparib maintenance treatment with an individualized starting dose in patients (Pts) with newly diagnosed advanced ovarian cancer (aOC) (1266)

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.

Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer

The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease. To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted). This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months. Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×103/μL [to convert to ×109/μL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy. The primary end point was blinded, independent central review-assessed PFS in the intention-to-treat population. A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events. This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting. ClinicalTrials.gov Identifier: NCT03709316.

PARP Inhibitors in Ovarian Cancer: A Review.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the ovarian cancer (OC) treatment landscape. This narrative review provides a comprehensive overview of data for the PARPis olaparib, niraparib, and rucaparib in patients with OC and discusses their role in disease management, with a focus on the use of PARPis as maintenance therapy in the United States (US). Olaparib was the first PARPi to be approved as first-line maintenance monotherapy in the US, with maintenance niraparib subsequently approved in the first-line setting. Data also support the efficacy of rucaparib as first-line maintenance monotherapy. PARPi maintenance combination therapy (olaparib plus bevacizumab) also provides benefit in patients with newly diagnosed advanced OC whose tumors tested positive for homologous recombination deficiency (HRD). Biomarker testing is critical in the newly diagnosed setting to identify patients most likely to benefit from PARPi maintenance therapy and guide treatment decisions. Clinical trial data support the use of PARPis (olaparib, niraparib, rucaparib) as second-line or later maintenance therapy in patients with platinum-sensitive relapsed OC. Although distinct differences in tolerability profile were observed between PARPis, they were generally well tolerated, with the majority of adverse events managed by dose modification. PARPis had no detrimental effect on patients' health-related quality of life. Real-world data support the use of PARPis in OC, although some differences between PARPis are apparent. Data from trials investigating novel combination strategies, such as PARPis plus immune checkpoint inhibitors, are awaited with interest; the optimal sequencing of novel therapies in OC remains to be established.

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

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

Real-world overall survival in second-line maintenance niraparib monotherapy vs active surveillance in BRCA wild-type patients with recurrent ovarian cancer.

5592 Background: The Phase 3NOVA trial assessed niraparib versus placebo as a maintenance treatment (tx) for patients (pts) with recurrent ovarian cancer (OC) who were platinum-sensitive after ≥2 regimens; progression-free survival was the primary endpoint and overall survival (OS) was a secondary endpoint (NCT01847274). The aim of this real-world study was to compare OS in a breast cancer gene wild-type ( BRCAwt) population of pts with recurrent OC and who received second-line maintenance (2Lm) niraparib monotherapy or were under active surveillance (AS). Methods: This study used the US nationwide Flatiron Health de-identified electronic health record (EHR)-derived database. Pts diagnosed with epithelial OC between 1Jan2011–31May2021 who completed 2L therapy between 1Jan2017–2Mar2022 were eligible for inclusion. Pts were BRCAwt, had an ECOG PS score 0–1, epithelial histology, and platinum-sensitive disease with ≥6 months between end of first-line tx and start of 2L tx. Pts were assigned to 2Lm niraparib or AS cohorts based on their management following 2L non-maintenance therapy (≤120 days). Follow-up was measured from the index date (end of 2L non-maintenance therapy) until end of study (31May2022), last activity, or death, whichever came first. A target trial emulation cloned inverse probability of censoring weighting (IPCW) methodology was selected a priori to minimize bias. IPCW median OS and hazard ratios (HR) for 2Lm versus AS were estimated with Kaplan-Meier curves and Cox regression models. Results: Overall, 266 BRCAwt pts were included and received niraparib 2Lm (N=123) or were under AS (N=143). Across 2Lm and AS cohorts, prior to cloning and IPCW, 23.6% and 34.3% of pts were aged ≥75 years, and 26.0% and 16.8% had an EHR value for race as other than White, respectively. The majority of pts were from community practice (80.5% and 90.2%, respectively), had serous OC (79.7% and 81.1%) and had Stage III disease (53.7% and 60.8%). Homologous recombination deficiency status was unknown for 92.7% and 86.0% of pts in 2Lm and AS cohorts, respectively. Median follow-up for 2Lm and AS cohorts was 16.8 (Quartile [Q] 1, Q3: 10.4, 28.7) and 10.2 (Q1, Q3: 4.1, 23.7) months, respectively. IPCW median OS was 28.1 (95% confidence interval [CI]: 22.5, 43.2) and 21.5 (95% CI: 14.7, 27.0) months (HR: 0.63 [95% CI: 0.45, 0.88]) for niraparib 2Lm and AS cohorts, respectively and survival rates at 24 months were 58.2% (95% CI: 47.5, 67.6) and 46.1% (95% CI: 33.6, 57.7). Conclusions: This analysis provides real-world data on OS among pts with OC receiving niraparib 2Lm or under AS in the 2L setting following chemotherapy. Funding: GSK study (219306). Editorial support was provided by Fishawack Health, funded by GSK.

Efficacy and safety of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer who had measurable residual disease: A post-hoc subgroup analysis of the PRIME study.

5562 Background: Niraparib maintenance therapy significantly prolonged progression-free survival (PFS) versus placebo in patients with newly diagnosed advanced ovarian cancer (aOC), but its antitumor activity remains unclear in those with measurable residual disease (MRD) after first-line platinum-based chemotherapy (1LCT). This study aims to report the efficacy, including antitumor activity, and safety of niraparib maintenance therapy in patients with MRD after 1LCT from the phase 3 PRIME trial (NCT03709316). Methods: In PRIME, adults with newly diagnosed aOC who had received cytoreductive surgery and responded to 1LCT were randomized 2:1 to receive niraparib or placebo with stratification by receipt of neoadjuvant chemotherapy, response to 1LCT, status of germline BRCA mutations, and tumor homologous recombination deficiency status. Tumor assessment was conducted at baseline and every 12 weeks thereafter by blinded independent central review (BICR) according to RECIST, version 1.1. Between 29 June 2018 and 11 November 2019, 384 patients were randomized (255 niraparib, 129 placebo). The data cut-off date was 30 September 2021. This post-hoc analysis reports BICR-assessed objective response rate (ORR) and PFS in patients with MRD at baseline. An initial response was confirmed ≥4 weeks later. Results: In total, 73 (19.0%) patients (47 niraparib, 26 placebo) had MRD at baseline. Baseline characteristics were well balanced between the two MRD groups. Complete and partial responses, both confirmed, were observed in 12 (25.5%) and 15 (31.9%) niraparib-treated patients and 3 (11.5%) and 5 (19.2%) placebo-treated patients, respectively, leading to a confirmed ORR of 57.4% with niraparib and 30.8% with placebo (odds ratio, 3.20; 95% confidence interval [CI], 1.11–9.11). ORRs by biomarker status are provided in the table. Median PFS (95% CI) was 22.3 (8.7–not estimable) months with niraparib versus 8.3 (5.6–11.0) months with placebo (hazard ratio, 0.36; 95% CI, 0.19–0.71). Treatment-emergent adverse events (TEAEs) of grade ≥3 occurred in 28 (59.6%) niraparib-treated patients and 7 (26.9%) placebo-treated patients. TEAEs led to treatment discontinuation in three (6.4%) niraparib-treated patients and one (3.8%) placebo-treated patient. Conclusions: In patients with newly diagnosed aOC who had MRD after 1LCT, niraparib maintenance therapy tended to induce additional antitumor activity and led to a clinically meaningful increase in PFS versus placebo. Clinical trial information: NCT03709316 .[Table: see text]

First trial of chemotherapy de-escalation in ovarian cancer (OC): A phase III randomized, open label study of niraparib maintenance after carboplatin and paclitaxel in patients with optimally debulked advanced (homologous recombination deficient) HRD high-grade ovarian cancer in first line therapy (N-PLUS/NOGGO-ov53/ENGOT-ov62).

TPS5620 Background: OC is the fifth most common cause of death from cancer in women. More than 70% of the patients are diagnosed with advanced disease and less than 40% of women with OC are cured. Currently, the standard therapy in HRD OC is surgical debulking followed by 6 cycles of chemotherapy with subsequent maintenance treatment with poly ADP ribose polymerase (PARP) inhibitors. Within the last decades, no focus was set on the benefits of fewer cycles of chemotherapy, even though there is evidence for comparable efficacy and less toxicity in comparison to more cycles. Chemotherapies are usually associated with side effects, which can be severe and even lead to therapy discontinuation. The data available about the needed number of chemotherapy cycles is weak, especially in the context of PARP inhibition. Furthermore, patients with stage III/IV with optimal cytoreduction are underrepresented in previous studies. In the N-PLUS trial, we hypothesize that recurrence-free survival (RFS) in patients receiving 3 cycles of chemotherapy followed by maintenance with niraparib is not inferior to 6 cycles of chemotherapy followed by niraparib in advanced HRD high-grade OC patients with no visible disease following primary tumor debulking. Methods: In this multicenter, randomized, open-label study 650 patients with advanced HRD high-grade OC with no residual tumor mass following primary tumor debulking will be enrolled. Patients will be randomized 1:1 to receive either 3 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm A) or 6 cycles carboplatin + paclitaxel and maintenance therapy with niraparib (Arm B) for a maximum of 36 months. Randomization will be performed according to the results of the NGS analysis and stratified either to BRCAm/LOH-independent or BRCAwt/LOHhigh, FIGO stage III vs. IV, and participating countries. The primary endpoint will be RFS, secondary endpoints will be OS, TFST, TWIST, PFS2, Quality of Life and safety assessments. Clinical trial information: NCT05460000 .

Real-world outcomes of first-line maintenance with niraparib or bevacizumab in advanced ovarian cancer.

e17598 Background: Niraparib and bevacizumab are the only FDA-approved first-line maintenance (1LM) therapies for advanced ovarian cancer (AOC) without a biomarker requirement. However, little information exists regarding the effectiveness of these treatments in the real world. Methods: We identified 89 AOC patients from the US-based deidentified Integra PrecisionQ database who received 1LM bevacizumab (n=31) or niraparib (n=58) following induction chemotherapy (CT) ± bevacizumab initiated between July 1, 2019, and March 31, 2021, and followed them until the data cut-off of March 31, 2022. Using the start of maintenance therapy as the index date, we examined patient characteristics, time to next treatment or death (TTNT; often used as a real-world proxy for progression-free survival), and overall survival (OS) for these treatment groups. Results: For patients who received 1LM bevacizumab, the median age was 69 years, 65% had Stage III cancer at index date, 84% had Eastern Cooperative Oncology Group (ECOG) performance status 0–1, and 87% received CT + bevacizumab as first-line therapy. For patients who received 1LM niraparib, the median age was 68.5 years, 66% had Stage III cancer at index date, 88% had an ECOG performance status of 0–1, and 79% received chemotherapy alone as first-line therapy. Only 1 bevacizumab (BRCAm) and 11 niraparib (4 BRCAm, 7 BRCAwt HRd) patients had known homologous recombination deficiency (HRd)-positive tumors. Patients treated with bevacizumab had a median TTNT of 4.5 months (mo) and a 12-month OS mark of 83.6%; for patients treated with niraparib, the corresponding values were 9.9 mo and 96.3%. Conclusions: Our study provides real-world outcomes data for newly diagnosed AOC patients receiving maintenance niraparib or bevacizumab following CT +/- bevacizumab. HRd testing results were only available for 19% of bevacizumab- and 40% of niraparib-treated patients, highlighting a need for greater testing in the real world. Future studies should examine which patient characteristics are associated with long-term survival for these and other treatment options to aid in the decision-making process. Funding: GSK215281. [Table: see text]

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.

Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer

PurposeTo report updated long-term efficacy and safety from the double-blind, placebo-controlled, phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). MethodsPatients with newly diagnosed advanced ovarian cancer with complete or partial response (CR or PR) to first-line platinum-based chemotherapy received niraparib or placebo once daily (2:1 ratio). Stratification factors were best response to first-line chemotherapy regimen (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient [HRp] or not determined). Updated (ad hoc) progression-free survival (PFS) data (as of November 17, 2021) by investigator assessment (INV) are reported. ResultsIn 733 randomised patients (niraparib, 487; placebo, 246), median PFS follow-up was 3.5years. Median INV-PFS was 24.5 versus 11.2months (hazard ratio, 0.52; 95% confidence interval [CI], 0.40–0.68) in the HRd population and 13.8 versus 8.2months (hazard ratio, 0.66; 95% CI, 0.56–0.79) in the overall population for niraparib and placebo, respectively. In the HRp population, median INV-PFS was 8.4 versus 5.4months (hazard ratio, 0.65; 95% CI, 0.49–0.87), respectively. Results were concordant with the primary analysis. Niraparib-treated patients were more likely to be free of progression or death at 4years than placebo-treated patients (HRd, 38% versus 17%; overall, 24% versus 14%). The most common grade ≥ 3 treatment-emergent adverse events in niraparib patients were thrombocytopenia (39.7%), anaemia (31.6%), and neutropenia (21.3%). Myelodysplastic syndromes/acute myeloid leukaemia incidence rate (1.2%) was the same for niraparib- and placebo-treated patients. Overall survival remained immature. ConclusionsNiraparib maintained clinically significant improvements in PFS with 3.5years of follow-up in patients with newly diagnosed advanced ovarian cancer at high risk of progression irrespective of HRD status. No new safety signals were identified.

A phase II single-arm trial of niraparib in platinum-sensitive metastatic castration-resistant prostate cancer with DNA repair defects (PLATPARP).

TPS291 Background: Platinum-based chemotherapy, either as monotherapy or in combination with taxanes, is increasingly used for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring germline and/or somatic homologous recombination repair gene mutations (HRRm). However, clinical responses with platinum-based therapy are often of limited duration and limited by cumulative toxicities. The PARP inhibitor (PARPi) olaparib is approved for the treatment of mCRPC patients with pathogenic HRRm after progression on enzalutamide or abiraterone. Importantly, sensitivity to platinum-based chemotherapy may predict improved clinical outcomes with PARPi, and ‘maintenance’ PARPi strategies are routinely used in patients with advanced ovarian and pancreatic malignancies with HRRm with initial clinical response to platinum chemotherapy. We hypothesize that maintenance niraparib, a PARPi with demonstrated activity in mCRPC with HRRm, will prolong clinical responses to platinum-based chemotherapy with acceptable toxicity in mCRPC patients harboring germline and/or somatic HRRm. Methods: We are conducting an open-label, single-arm, phase II study to evaluate the clinical benefit of maintenance niraparib in biomarker-defined, platinum-sensitive mCRPC patients. Eligible subjects harbor a pathogenic germline and/or somatic mutation in BRCA1/2, ATM, FANCA, CDK12, RAD51B, RAD54L, PALB2, CHEK2, HDAC2, or BRIP1 and have received at least 3 cycles (or minimum 9 weeks) of platinum-based chemotherapy for the treatment of mCRPC per investigator discretion. Following ³4 weeks since completion of chemotherapy, subjects without evidence of clinical or radiographic disease progression receive investigational treatment with maintenance niraparib (starting dose 200 mg daily). The primary objective is an improvement in 6 month PFS rate (PFS6) (H0: PFS6 rate 25%; H1: PFS6 rate 50%; power 0.77 with one-sided α = 0.05). Serial plasma samples are obtained for correlative analyses of markers of response and/or resistance to maintenance niraparib. Eight of a planned total of 18 subjects have enrolled (N=3 germline BRCA2; N=2 somatic BRCA2; N=1 germline PALB2; N=1 germline ATM; N=1 germline CHEK2). This study incorporates a novel, combined genetic and clinical patient-selection approach for PARPi therapy to optimize clinical outcomes. Clinical trial information: NCT04288687 .

Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study.

There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. Ki67 at diagnosis did not discriminate responders to PARPi.

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.

43P Time to next treatment (TTNT) of first-line maintenance (1Lm) niraparib monotherapy in epithelial ovarian cancer (EOC) patients (pts) in the CHAR1ZMA study

43P Time to next treatment (TTNT) of first-line maintenance (1Lm) niraparib monotherapy in epithelial ovarian cancer (EOC) patients (pts) in the CHAR1ZMA study