Niraparib Maintenance Research Articles

738P Quality-adjusted time without symptom or toxicity (QA-TWiST) and quality-adjusted progression-free survival (QA-PFS) of first-line (1L) maintenance niraparib in patients with advanced ovarian cancer (OC): Results from the PRIMA trial

The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) phase III trial showed niraparib significantly prolongs median PFS vs placebo in patients with advanced OC responsive to 1L platinum (Pt)-based chemotherapy (CT), regardless of biomarker status. This post hoc analysis of PRIMA examined the QA-TWiST and QA-PFS of patients on maintenance niraparib vs placebo.

746P Real-world clinical outcomes of patients with de novo advanced high-grade epithelial ovarian cancer eligible to niraparib maintenance in France

PARP inhibitors (PARPi) demonstrated improvement in progression-free survival (PFS) following first-line (1L) platinum-based chemotherapy (Pt-CT) for advanced ovarian carcinoma (OC) patients (pts). Here we describe real-world clinical outcomes in pts with de novo high-grade epithelial OC (HGEOC) eligible for niraparib per EMEA approval (PRIMA trial).

Overtreatment and excessive cost associated with primary versus secondary PARP inhibitor (PARPi) maintenance therapy for ovarian/peritoneal/fallopian tube cancer (EOC)

Objectives: To determine the efficacy and cost of primary olaparib or niraparib maintenance versus secondary olaparib or niraparib maintenance in platinum sensitive EOC. Methods: An institutional review board (IRB) approved single institution retrospective cohort study was performed in women with EOC to determine the efficacy and cost of primary or secondary maintenance PARPi therapy. We determined the costs of olaparib and niraparib therapy based on previously published costs of therapy and duration of therapy based on the Solo 1/ Solo 2 and Prima and Nova trials, respectively. Results: Among 40 patients treated with PARPi after 1 or 2 platinum chemotherapy there was no difference in overall survival (p=0.97) Among 166 women with stage III/IV germ-line BRCA mutated EOC who were followed >3 years following chemotherapy without PARPi therapy, 28.8% were disease free for more than 3 years (18.6% never recurred and 10.2% recurred >3 years after chemotherapy). Among 193 patients without a BRCA mutation 20.2% did not recur and 12 (6.2%) recurred more than 3 years after their chemotherapy. Primary olaparib maintenance therapy was significantly more expensive than secondary olaparib maintenance therapy by 260%. Primary niraparib maintenance therapy was slightly more expensive than secondary niraparib maintenance therapy by 4%, 51%, and 15% for BRCA mutated, HR deficient, and HR proficient patients, respectively. Notably, by eliminating the overtreatment of patients with primary PARPi therapy, the cost of delayed maintenance treatment for 100 women with EOC with BRCA mutations would be associated with a cost savings of $37,335,360 for olaparib and $7,335,360 for niraparib. Download : Download high-res image (89KB) Download : Download full-size image Conclusions: In this retrospective cohort of women with EOC, up to 29% percent of BRCA mutated patients may be over treated with primary PARPi maintenance therapy with significantly increased treatment costs.

Efficacy of niraparib by timing of surgery and residual disease: a post-hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study

<h3>Objectives:</h3> Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved as maintenance treatment for patients (pts) with newly diagnosed advanced or recurrent ovarian cancer following a response to platinum-based chemotherapy (CT) doublet. The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study showed that niraparib following first-line treatment improved progression-free survival (PFS) in the overall intention-to-treat (ITT) population (hazard ratio [HR] 0.62; 95% CI 0.50-0.76). <h3>Methods:</h3> This double-blind, placebo (PBO)-controlled, phase 3 trial evaluated niraparib in pts with newly diagnosed, advanced, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response to first-line CT. Pts were considered to be at a high risk for disease progression based on their clinical characteristics. This post-hoc analysis presents the efficacy of niraparib, measured by PFS, based on time of surgery and residual disease status, and was not powered to determine differences among the subgroups. <h3>Results:</h3> Data cutoff was May 2019. In total, 733 pts were randomized in the PRIMA study. Efficacy outcomes by surgical timing, either primary debulking surgery (PDS) or interval debulking surgery (IDS), and postoperative residual disease status, either no visible residual disease (NVRD) or visible residual disease (VRD), are shown in Table. Pts who underwent PDS or IDS had similar efficacy with niraparib maintenance treatment versus PBO in the ITT population (PFS HRs were 0.67 and 0.57, respectively). Niraparib treatment reduced risk of progression by 42% in pts who received PDS and had VRD, 35% in those with IDS and NVRD, and 59% in those with IDS and VRD. Efficacy was not evaluable for pts with PDS and NVRD due to low sample size. <h3>Conclusions:</h3> In this post-hoc analysis, the impact of residual disease after PDS or IDS on the efficacy of niraparib was comparable across subgroups. Pts with IDS and VRD had the highest reduction in the risk of progression

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer and a time-to-progression after penultimate platinum-based chemotherapy of 6-12 or >12 months: a subgroup analysis of the phase III NORA trial

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer and a time-to-progression after penultimate platinum-based chemotherapy of 6-12 or >12 months: a subgroup analysis of the phase III NORA trial

Evaluation of treatment response to niraparib in patients with platinum-sensitive recurrent ovarian cancer and measurable lesions at baseline: a sub-analysis of the phase III NORA trial

<h3>Objectives:</h3> This sub-analysis investigated treatment response to niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer (PSROC) included in the NORA trial who had measurable lesions after finishing chemotherapy and before initiating niraparib. <h3>Methods:</h3> In the double-blind, phase III NORA trial, 265 adult (≥18 years) Chinese women with PSROC were randomised 2:1 to receive oral niraparib (n=177; 300 mg/day, patients with bodyweight <77 kg or platelet count <150×10³/µL received 200 mg/day) or matched placebo (n=88)(NCT03705156). The primary endpoint was progression-free survival (PFS). This sub-analysis assessed treatment outcomes among patients with measurable lesions after finishing chemotherapy and before initiating niraparib maintenance therapy. Baseline disease assessment (before niraparib initiation) and subsequent tumour response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review (BICR). In patients with measurable lesions at baseline, the objective response rate (ORR) was evaluated. Odds ratios (OR) were adjusted for response to previous platinum-based chemotherapy and time to disease progression following the penultimate platinum-based chemotherapy, and were calculated using logistic regression. Adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. <h3>Results:</h3> Of the 265 patients included in the NORA study, 64 (24.2%) had measurable lesions at baseline (niraparib, n=43; placebo, n=21), 21.9% (14/64) of whom had received secondary cytoreductive surgery before the last round of chemotherapy. Among patients with measurable lesions, those who received niraparib achieved a higher ORR compared with those receiving placebo (32.6 vs 14.3%; OR=2.7, 95% CI, 0.67-11.18), and niraparib also led to a higher ORR regardless of germline <i>BRCA</i> mutation status (g<i>BRCA</i> mutation: 50.0 vs 28.6%, non-g<i>BRCA</i> mutation: 25.8 vs 7.1%) (Table). Niraparib was well tolerated by patients in this sub-analysis, with a safety profile in-line with previous reports. <h3>Conclusions:</h3> Among patients included in the NORA study with measurable lesions at baseline, niraparib maintenance therapy induced additional antitumour activity versus placebo, with a higher ORR regardless of germline <i>BRCA</i> mutation status, and was well tolerated. The high rates of tumour response observed for niraparib-treated patients in the NORA study further support the role of niraparib as maintenance treatment for patients with PSROC and measurable lesions after chemotherapy.

Efficacy and safety of niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer with complete or partial response to the last platinum-based chemotherapy: a subgroup analysis of the phase III NORA trial

Efficacy and safety of niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer with complete or partial response to the last platinum-based chemotherapy: a subgroup analysis of the phase III NORA trial

Precision medicine for hereditary tumors in gynecologic malignancies.

Genomic medicine for gynecologic tumors is characterized by hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS). Poly ADP-ribose polymerase (PARP) inhibitor, olaparib, and the immune checkpoint inhibitor, pembrolizumab, which are drugs that show sensitivity to each hereditary tumor, have begun to spread in clinical practice for gynecologic malignancies. In clinical use, platinum sensitivity is used as a clinical surrogate marker for olaparib sensitivity, and microsatellite instability is used as a biological surrogate marker for pembrolizumab sensitivity. BRCA genetic testing and microsatellite instability test have been used as companion diagnostics before starting olaparib and pembrolizumab treatment, respectively. Homologous recombination deficiency test could be used for companion diagnostic of olaparib combination with bevacizumab in first-line maintenance treatment and niraparib without re-administration of platinum agents in the treatment of recurrence. The approval of the three drugs has been changing the treatment of gynecologic malignancies. Furthermore, preventive medical care has been covered by insurance since April 2020 for breast and/or ovarian cancer patients with germline BRCA1/2 mutation in Japan. This review article outlines the current status and future prospects of precision medicine for gynecologic hereditary tumors focusing on HBOC and LS.

Safety assessment of niraparib individualized starting dose in patients with platinum-sensitive recurrent ovarian cancer: A randomized, double-blind, placebo-controlled, phase III NORA trial.

5535 Background: To present the safety profile of niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer (PSROC) included in the NORA trial. Methods: The double-blind, randomized, placebo-controlled, multicenter, phase III NORA trial (NCT03705156) included adult (≥18 years) Chinese women with PSROC who received ≥2 prior lines of platinum-based chemotherapy. Post ≤8 weeks of the last chemotherapy, patients were randomized (2:1) to receive oral niraparib (300 mg/day or 200 mg/day for patients with bodyweight &lt;77 kg or platelet count &lt;150 × 103/µL) or matched placebo. The primary endpoint was progression free survival, reported previously. Safety was assessed in terms of treatment emergent adverse events (TEAEs) related to hematologic toxicity (anemia/platelet count decreased and neutrophil count decreased) and non-hematologic toxicity (nausea/vomiting/constipation/insomnia/palpitations/hypertension). Adverse events (AEs) were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. The data cutoff was February 1, 2020. Results: Of 265 patients included, the first 16 patients were given oral niraparib or matched placebo at a fixed starting dose of 300mg while 249 patients received individualized starting dose of niraparib (n = 166) or matched placebo (n = 83) based on baseline bodyweight and platelet count. The incidence of any TEAEs and grade ≥3 TEAEs was 100% and 50.8%, respectively in niraparib group, while 95.5% and 19.3%, respectively in placebo. Incidence of all grades of hematologic toxicity, gastrointestinal adverse events (nausea, constipation and vomiting), insomnia, palpitation and hypertension were highest in the first month after treatment with a gradual decrease in the further months. The median time to onset of grade ≥3 anemia, decreased neutrophil count and decreased platelet count were 87, 28, and 22 days, respectively, in the niraparib group. In niraparib group, any TEAEs that lead to dose reduction was observed in 59.9% of patients. Only 2 (1.1%) patients discontinued the treatment due to platelet count decreased and no patients discontinued niraparib treatment due to anemia or neutrophil count decreased. Overall, only 4% of patients in the niraparib group and 5.7% in the placebo group discontinued the treatment due to TEAEs. Conclusions: The lower incidence of TEAEs and the discontinuation rates indicate improved safety profile of niraparib with individualized starting dose in PSROC. Clinical trial information: NCT03705156.

Real-life data of niraparib maintenance treatment in patients with recurrent platinum-sensitive ovarian cancer.

5560 Background: PARP (poly adenosine diphosphate [ADP]–ribose polymerase) inhibitors are the new standard for maintenance treatment in platinum sensitive recurrent ovarian cancer (PSROC), independent of germline (g-BRCA) or somatic BRCA mutation status. Real-life data after the introduction of new anti-neoplastic agents are needed to evaluate whether the benefit observed in phase III trials can be translated into clinical practice. The aim of this study was to provide real-life data on efficacy and safety of niraparib in non-gBRCA PSROC. Methods: This retrospective multi-center cohort study included patients with PSROC who were enrolled in a national individual patient access program in Norway. Efficacy and safety data were collected from the patients´ electronic medical records. The primary outcome was time from start of niraparib treatment to first subsequent treatment (TFST). Secondary endpoints included prevalence of dose interruption and -reduction, as well as adverse events. Results: The study included 106 patients with median age of 64 years (range 38-81). After median follow up of 15.3 months (95% CI 12.1-18.5), 71 patients (67%) had progressed, 64 (60%) had started a new line of treatment, and 25 (24%) had died. 25 (24%) patients were still receiving niraparib. Median duration of niraparib treatment was 7.6 months (0.4 to 27.3 months). Median TFST was 11.7 months (95% CI 9.2 -14.2). Patients with elevated CA125 after chemotherapy prior to start of niraparib had shorter progression-free survival (PFS) compared to patients with complete serological response (6.5 months (95% CI 5.7 – 7.3) vs 12 months (95% CI 6.2 – 17.9, (p &lt; 0.001)). Grade 3-4 hematologic and non-hematologic events occurred in 25% and 17% of the patients, respectively. The most common grade 3/4 hematologic events were anemia (15%), thrombocytopenia (11%) and neutropenia (8%). Adverse events led to dose interruption in 38% and dose reduction in 44% of the patients. Patients with individualized dosing based on baseline weight and platelet counts had fewer dose reductions (p &lt; 0.001) and -interruptions (p = 0.042) than patients whose dose was not adjusted to those baseline values. Conclusions: In a real-life setting, niraparib maintenance treatment in patients with non-gBRCA PSROC showed efficacy comparable with the published phase III data and an acceptable safety profile. Individualized dosing at start of treatment minimized adverse events. The prolonged PFS in patients with CA125 normalization after last chemotherapy, suggests that these patients in particular benefit from maintenance treatment but warrants confirmation in a larger sample.[Table: see text]

Efficacy of niraparib maintenance therapy in Chinese women with platinum-sensitive recurrent ovarian cancer with and without secondary cytoreductive surgery: Results from the NORA trial.

5534 Background: NORA is the first, phase III, randomized controlled trial (RCT) that demonstrated individualized starting dose regimen of niraparib, which significantly improved PFS in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC). This sub-group analysis evaluated the efficacy of niraparib maintenance therapy with and without secondary cytoreductive surgery (SCS) in PSROC. Methods: The NORA phase III RCT included adult (≥18 years) Chinese women with PSROC who were randomized in a 2:1 ratio to receive oral niraparib (n = 177) or matched placebo (n = 88). This retrospective subgroup analysis was based on the progression-free survival (PFS) of niraparib maintenance therapy in these two groups of patients with PSROC, patients with SCS, and patients without SCS. The PFS was assessed by blinded independent central review. The Kaplan-Meier (KM) estimator and log-rank test were performed to calculate the median PFS time. Results: Of the 265 evaluable patients, 69 (26.0%) patients received the SCS (niraparib, n = 48; placebo, n = 21), and 196 (74.0%) patients were without SCS (niraparib, n = 129; placebo, n = 67). Among patients with and without SCS, baseline characteristics for BRCA mutation were 26.1% vs 41.8%, complete response to last platinum-based chemotherapy were 68.1% vs 43.9%, time (6-12 months) to progression after penultimate therapy were 23.2% vs 34.7%, respectively. Treatment with niraparib led to a significant reduction of risk to disease progression compared with placebo in patients with SCS (Hazard ratio [95% CI]: 0.32 [0.13–0.78]; P = 0.0102) and without SCS (0.34 [0.23–0.50]; P&lt; 0.001). Moreover, in the subgroups of patients who received SCS, niraparib maintenance therapy had a significantly longer PFS compared with placebo (Median [95% CI]: not reached [18.33 – not estimable] vs 5.75 months [3.68 – not estimable]; P = 0.0102). This trend was also similar in the subgroup of patients who did not receive SCS (Median [95% CI]: 10.28 months [7.49 – 18.37] vs 4.90 months [3.71 – 5.52]; P &lt; 0.0001). Conclusions: The results from this retrospective sub-group analysis revealed that niraparib maintenance therapy provided significant clinical efficacy in patients with PSROC, irrespective of SCS. Clinical trial information: NCT03705156.

Niraparib efficacy and safety in patients with BRCA mutated (BRCAm) ovarian cancer: Results from three phase 3 niraparib trials.

5518 Background: Niraparib has been approved for the maintenance treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer after front-line chemotherapy (CT) and in the recurrent setting. Here, we summarize niraparib efficacy and safety in patients with BRCAm OC across three phase 3 trials: PRIMA/ENGOT-OV26/GOG-3012 (PRIMA; NCT02655016), ENGOT-OV16/NOVA (NOVA; NCT01847274), and NORA (NCT03705156). Methods: Patients enrolled in the PRIMA trial had newly diagnosed advanced ovarian, fallopian tube, or primary peritoneal cancer. All patients had stage III or IV high-grade serous or endometrioid tumors and had a complete or partial response to their first-line platinum-based CT treatment. Subgroup analysis by tumor BRCAm status was prespecified. Patients enrolled in the NOVA and NORA studies had platinum-sensitive, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. Patients had already received at least 2 lines of platinum-based CT regimens. In both studies, subgroup analysis by germline BRCAm status was prespecified. The primary endpoint in all trials was progression-free survival (PFS) by blinded independent central review. Results: The BRCAm populations from each trial are as follows: 223 (148 BRCA1m and 75 BRCA2m) from the PRIMA trial, 203 (128 BRCA1m, 69 BRCA2m, and 13 BRCA1/2m) from the NOVA trial, and 100 (78 BRCA1m, 21 BRCA2m, and 1 BRCA1/2m) from the NORA trial. PFS results are shown in the Table. Across the 3 trials, the most common treatment-emergent adverse events were thrombocytopenia, anemia, neutropenia, and hypertension. Conclusions: Patients with BRCAm OC derived a significant PFS benefit from niraparib maintenance treatment across all 3 trials. No new safety signals were identified. Clinical trial information: NCT02655016, NCT01847274, NCT03705156. [Table: see text]

Expectations and Challenges of First-Line Maintenance Therapy for Advanced Ovarian Cancer.

The incidence of ovarian cancer, which has had a poor prognosis, is increasing annually. Currently, the prognosis is expected to improve with the use of molecular-targeted drugs and immune checkpoint inhibitors as maintenance therapies after the first-line chemotherapy. The GOG218 and ICON7 studies reported the usefulness of bevacizumab and the SOLO-1 and PRIMA (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy) studies have reported the usefulness of olaparib and niraparib, respectively. The ATHENA study investigating the usefulness of rucaparib is currently ongoing. Although clinical studies of immune checkpoint inhibitors are lagging in the field of gynecology, many clinical studies using programmed death cell-1 (PD-1) and PD-1 ligand 1 (PD-L1) antibodies are currently ongoing. Some biomarkers have been identified for molecular-targeted drugs, but none have been identified for immune checkpoint inhibitors, which is a challenge that should be addressed in the future.

Niraparib in the maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: safety and efficacy

ABSTRACT Introduction: Approximately 300,000 women worldwide are diagnosed each year with ovarian cancer. Frequently diagnosed in late stages with ambiguous symptomatology, ovarian cancer has a low survival rate. Areas covered: Niraparib, a PARP inhibitor, was approved in 2020 for use in the maintenance treatment of ovarian cancer regardless of biomarker status. Included in the review are PRIMA (NCT02655016), NOVA (NCT01847274), AVANOVA2 (NCT02354131), and QUADRA (NCT02354586) trials which herald the advent of using maintenance oral therapies in the treatment of ovarian cancer. Additionally, with new combination drug trials, exciting avenues for treatment are also discussed with the FIRST (NCT03016338) trial. Expert opinion: Maintenance niraparib treatment regardless of genetic profile offers a new modality for the treatment of ovarian cancer with a low side effect profile and importantly oral dosing. New combinations of synergistic immunotherapeutics, and antiangiogenesis therapies with niraparib also offer exciting new frontiers for patients with ovarian cancer.

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆

This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer. In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150× 103/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n=177) or placebo (n= 88); 249 patients received an ISD (300 mg, n= 14; 200 mg, n= 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR)= 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%). Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

Population-adjusted indirect treatment comparison of maintenance PARP inhibitor with or without bevacizumab versus bevacizumab alone in women with newly diagnosed advanced ovarian cancer.

Background:In patients with newly diagnosed ovarian cancer, bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors, alone or in combination, have shown benefit as maintenance treatment following platinum-based chemotherapy. However, no trials have compared a PARP inhibitor plus bevacizumab versus a PARP inhibitor, or a PARP inhibitor versus bevacizumab. We performed an unanchored population-adjusted indirect treatment comparison to estimate the relative efficacy and safety of maintenance treatments for newly diagnosed advanced ovarian cancer.Methods:Analyses were performed using aggregate data from the PRIMA trial and patient-level data from a subset of patients from the PAOLA-1 trial that met surgery and staging eligibility criteria of PRIMA. Propensity weights were used to match baseline characteristics of the PAOLA-1 subset to those of the PRIMA population. Analysis was performed in overall (biomarker-unselected) and homologous recombination repair deficiency (HRD)-positive populations.Results:A total of 595/806 (266/387 HRD-positive) PAOLA-1 patients were included. After matching, the effective sample size for PAOLA-1 was 532 (242 HRD-positive). Maintenance olaparib plus bevacizumab reduced the risk of disease progression or death by 43% [hazard ratio (HR) 0.57; 95% confidence interval (CI): 0.47–0.69] versus niraparib and by 40% (HR 0.60; 95% CI: 0.49–0.74) versus bevacizumab in the biomarker-unselected population and by 43% (HR 0.57; 95% CI: 0.41–0.79) and 60% (HR 0.40; 95% CI: 0.29–0.55), respectively, in the HRD-positive population. Progression-free survival (PFS) benefits of maintenance niraparib and bevacizumab arms were comparable in the biomarker-unselected population (HR 1.07; 95% CI: 0.87–1.32); however, niraparib showed a 30% reduced risk compared with bevacizumab (HR 0.70; 95% CI: 0.51–0.97) in the HRD-positive population.Conclusions:In biomarker-unselected and HRD-positive patients, combination treatment with olaparib plus bevacizumab as maintenance treatment improves PFS for women with newly diagnosed advanced ovarian cancer compared with either bevacizumab or niraparib alone. Results are hypothesis generating and could guide randomised trial design.

A phase III, randomized, double blinded trial of platinum based chemotherapy with or without atezolizumab followed by niraparib maintenance with or without atezolizumab in patients with recurrent ovarian, tubal, or peritoneal cancer and platinum treatment free interval of more than 6 months: ENGOT-Ov41/GEICO 69-O/ANITA Trial

BackgroundPlatinum based chemotherapy is the treatment of choice for ovarian cancer patients with a platinum treatment free interval of >6 months. Niraparib is an oral poly (ADP-ribose) polymerase inhibitor approved...

Cost-effectiveness of Maintenance Therapy Based on Molecular Classification Following Treatment of Primary Epithelial Ovarian Cancer in the United States

There are large randomized clinical trials-SOLO-1 (Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy [December 2018]), PRIMA (A Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy [September 2019]), and PAOLA-1 (Platine, Avastin and Olaparib in 1st Line [December 2019])-reporting positive efficacy results for maintenance regimens for women with primary, advanced epithelial ovarian cancer. The findings resulted in approval by the US Food and Drug Administration of the treatments studied as of May 2020. However, there are pressing economic considerations given the many eligible patients and substantial associated costs. To evaluate the cost-effectiveness of maintenance strategies for patients with (1) a BRCA variant, (2) homologous recombination deficiency without a BRCA variant, or (3) homologous recombination proficiency. In this economic evaluation of the US health care sector using simulated patients with primary epithelial ovarian cancer, 3 decision trees were developed, one for each molecular signature. The maintenance strategies evaluated were olaparib (SOLO-1), olaparib-bevacizumab (PAOLA-1), bevacizumab (PAOLA-1), and niraparib (PRIMA). Base case 1 assessed olaparib, olaparib-bevacizumab, bevacizumab, and niraparib vs observation of a patient with a BRCA variant. Base case 2 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination deficiency without a BRCA variant. Base case 3 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination proficiency. The time horizon was 24 months. Costs were estimated from Medicare claims, wholesale acquisition prices, and published sources. Probabilistic sensitivity analyses with microsimulation were then conducted to account for uncertainty and assess model stability. One-way sensitivity analyses were also performed. The study was performed from January through June 2020. Incremental cost-effectiveness ratios (ICERs) in US dollars per progression-free life-year saved (PF-LYS). Assuming a willingness-to-pay threshold of $100 000/PF-LYS, none of the drugs could be considered cost-effective compared with observation. In the case of a patient with a BRCA variant, olaparib was the most cost-effective (ICER, $186 777/PF-LYS). The third-party payer price per month of olaparib would need to be reduced from approximately $17 000 to $9000 to be considered cost-effective. Olaparib-bevacizumab was the most cost-effective in the case of a patient with homologous recombination deficiency without a BRCA variant (ICER, $629 347/PF-LYS), and bevacizumab was the most cost-effective in the case of patient with homologous recombination proficiency (ICER, $557 865/PF-LYS). Even at a price of $0 per month, niraparib could not be considered cost-effective as a maintenance strategy for patients with homologous recombination proficiency. The findings of this study suggest that, at current costs, maintenance therapy for primary ovarian cancer is not cost-effective, regardless of molecular signature. For certain therapies, lowering the drug price alone may not make them cost-effective.

Niraparib maintenance in frontline management of ovarian cancer: a cost effectiveness analysis

ObjectivesNiraparib maintenance after frontline chemotherapy for advanced ovarian cancer extends progression free survival. The objective of this study was to determine the cost effectiveness of niraparib maintenance therapy in patients...

Cost-effectiveness of various maintenance therapies based on mutation status following first-line treatment of primary epithelial ovarian cancer in the United States.

e19399 Background: The recent SOLO1, PRIMA, and PAOLA trials all reported positive efficacy results, making it difficult to determine optimal upfront maintenance therapy for patients with primary, advanced ovarian cancer. We evaluated the cost-effectiveness of the maintenance strategies outlined in these trials for BRCA-positive patients, homologous-recombination deficient patients without a BRCA mutation (HRD-positive), and homologous-recombination proficient (HRD-negative) patients. Methods: Three decision analysis models were developed, one for each mutation status. We evaluated olaparib (SOLO1), olaparib/bevacizumab (PAOLA), bevacizumab alone (PAOLA), and niraparib (PRIMA) maintenance strategies. Base case 1 assessed olaparib vs olaparib/bevacizumab vs bevacizumab vs niraparib vs no maintenance therapy in BRCA-positive patients. Base cases 2 and 3 assessed olaparib/bevacizumab vs bevacizumab vs niraparib vs no maintenance therapy in HRD-positive and HRD-negative patients, respectively. Time horizon was 24 months. Costs, measured in U.S. dollars, were estimated from Medicare claims, wholesale acquisition prices, and previously published sources. Incremental cost-effectiveness ratios (ICERs) were in dollars per progression-free life-year saved (PF-LYS). One-way sensitivity analyses were performed varying drug cost and progression-free survival. Results: Assuming a willingness-to-pay threshold of $100,000/PF-LYS, none of the drug maintenance strategies could be considered cost effective compared with observation. In BRCA-positive patients (base case 1), olaparib monotherapy was the most cost-effective strategy, yielding an ICER of $181,059/PF-LYS. The third-party payer cost per 28-day supply of olaparib would need to be reduced from approximately $17,000 to $9,200 to be considered cost effective compared with observation. In HRD-positive patients (base case 2) and HRD-negative patients (base case 3), bevacizumab monotherapy was the most cost-effective option, with ICERs of $326,491/PF-LYS and $253,937/PF-LYS respectively. Conclusions: At current costs, maintenance therapy for primary ovarian cancer is not cost effective, regardless of mutation status. In BRCA-positive women, lowering the cost of olaparib may make it cost effective compared with observation.