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The economic impact of adverse events (AEs) for poly (ADP-ribose) polymerase inhibitors (PARPis) in ovarian or breast cancer has not been widely evaluated. Compare PARPi-related AE management costs from a US payer perspective. The frequency of treatment-related grade 3–4 AEs was obtained from published clinical trials of PARPis for the treatment of advanced ovarian cancer (AOC), platinum-sensitive recurrent ovarian cancer (PSROC), and metastatic breast cancer (MBC). AE management costs per patient (2020 USD) per treatment course were calculated by multiplying the AE unit costs by the frequency of AEs for each arm of each trial. Sensitivity analyses were conducted according to the lower and upper limits of the 95% confidence interval for AE rates and unit costs, respectively. Scenarios were also performed to explore the uncertainty of outcomes. Total AE management costs in AOC were: $3,904, olaparib; $5,595, olaparib plus bevacizumab; and $12,215, niraparib. In PSROC, total costs were: $3,894, olaparib; $6,001, rucaparib; and $11,492, niraparib, and in MBC: $3,574, olaparib; and $9,489, talazoparib. Hematological toxicities were the key drivers of AE management costs for PARPis. The main AEs among PARPis were hematological. Olaparib was associated with lower AE costs compared to other PARPis. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the fifth leading cause of cancer death in women in the US. With poly(ADP-ribose) polymerase (PARP) inhibitors having shown promising results in ongoing trials, there is interest in better understanding their economic value. Objective: This study aimed to review and evaluate the quality of published cost-effectiveness analyses (CEAs), and provide recommendations for CEAs in this setting. Methods: A systematic literature review of the MEDLINE and EMBASE databases was conducted in June 2019 to identify CEAs of PARP inhibitors in treating advanced ovarian cancer from peer-reviewed journals and conferences. Key information from the identified publications were extracted and reviewed. The quality of full-text studies was assessed using the Quality of Health Economic Studies instrument. Recommendations for future CEAs were developed based on the findings from the literature review. Results: Eighteen CEAs (five in full texts) met the inclusion criteria. Most adopted a US healthcare or societal perspective. The majority of the studies did not clearly display the economic model structure. No studies reported the validation of model projections based on internal or external data. Surrogate outcomes such as incremental costs per progression-free life-year gained were the most common outcomes reported. The majority of studies drew their conclusions based on surrogate outcomes, even with no theoretical or empirical threshold for cost effectiveness. All five full-text studies included some type of sensitivity or scenario analyses. The key drivers of the incremental cost-effectiveness ratio were treatment duration, effects, and costs, health utility, and prevalence of BRCA mutations. Conclusion: In the existing CEAs for PARP inhibitors, there were uncertainties and challenges leading to variation in quality. We provided recommendations to improve consistency and quality of CEAs in this setting, which will help to better understand the value of PARP inhibitors, improve decision making, and reduce potential misallocation of resources. [ABSTRACT FROM AUTHOR]

This study evaluated the cost-effectiveness of olaparib monotherapy in the first-line maintenance setting vs. surveillance in women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation from a US third-party payer perspective. A three-state (progression free, progressed disease, and death) partitioned survival model over a 50-year lifetime horizon was developed. Piecewise models were applied to data from the phase III trial SOLO1 to extrapolate survival outcomes. Health state utilities and adverse event disutilities were obtained from literature and SOLO1. Treatment costs, adverse event costs, and medical costs associated with health states were obtained from publicly available databases, SOLO1, and real-world data. Time on treatment was estimated using the data from SOLO1. Incremental costs per quality-adjusted life year (QALY) and life year (LY) gained were estimated. One-way deterministic and probabilistic sensitivity analyses were conducted. Over a lifetime horizon, olaparib was associated with an additional 3.63 LYs and 2.93 QALYs, and an incremental total cost of $152,545 vs. surveillance. Incremental cost per LY gained and per QALY gained for olaparib were $42,032 and $51,986, respectively. The incremental cost-effectiveness ratios remained below $100,000 across a range of inputs and scenarios. In the PSA, the probability of olaparib being cost-effective at a $100,000 per QALY threshold was 99%. Compared to surveillance, olaparib increases both the LYs and QALYs of women with newly diagnosed advanced ovarian cancer and with a germline or somatic BRCA mutation. Olaparib offers a cost-effective maintenance option for these women from a US third-party payer perspective. • Olaparib is predicted to increase the LYs and QALYs of women with advanced BRCA associated ovarian cancer vs. surveillance • First-line maintenance olaparib is cost-effective over a lifetime horizon compared to surveillance • The cost-effectiveness of olaparib was robust across a range of plausible input values and alternative scenarios [ABSTRACT FROM AUTHOR]

The addition of maintenance olaparib to bevacizumab (OLAP+BEV) demonstrated significant progression-free survival (PFS) benefit vs BEV alone in the randomized trial PAOLA-1 in advanced ovarian cancer patients with homologous recombination deficiency (HRD)-positive tumors. We aim to quantify the health and economic impact by evaluating the US cost-effectiveness of OLAP+BEV relative to BEV as a maintenance treatment for women with advanced ovarian cancer who had partial or complete response to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status Our economic model was a cohort-level four state partitioned survival model with a lifetime horizon. States were progression-free, post first progression, post second progression, and death, modelled using first PFS (PFS1), second PFS (PFS2) and overall survival (OS) outcomes from the PAOLA-1 trial. This approach captured multiple progressions, and the differing health state utility after each progression. PFS1 was modelled through parametric mixture survival modeling to a landmark survival point at 5 years, beyond which, patients who have not progressed are assumed to experience all-cause mortality as the general population. PFS2 and OS were modelled by fitting standard parametric models, and time on treatment data was used directly from PAOLA-1, with a treatment cap of 24 months for OLAP and 15 months for BEV. The cost of HRD testing was calculated as unit cost divided by prevalence and was included as a one-time cost for OLAP+BEV arm. US-based health state utility values were analyzed by applying the methods developed by Pickard. The analyses were conducted from a US healthcare payer perspective, with an annual discount rate of 3%. We also explored the robustness of results using deterministic (DSA) and probabilistic sensitivity analysis. At year 5, 45.1% and 16.9% patients remained PFS from OLAP+BEV and BEV arm, respectively. The results showed that compared with bevacizumab alone, OLAP+BEV led to a gain in quality-adjusted life years (2.89 QALYs gain) and life years (3.43 Lys gain) but resulted in higher costs, leading to a deterministic incremental cost-effectiveness ratio (ICER) of $75,276 per QALY. OLAP+BEV had an 87.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. DSA identified efficacy (PFS and OS parameters), subsequent treatment and utility values as key model drivers. [Display omitted] OLAP+BEV is associated with LY and QALY gain, and is cost effective for US payers relative to BEV monotherapy for the treatment of women with advanced, HRD-positive ovarian cancer [ABSTRACT FROM AUTHOR]

Objectives: Multiple poly-ADP ribose polymerase inhibitor (PARPi) maintenance treatment (mTx) options are available for patients with advanced ovarian cancer after response to first-line platinum chemotherapy (PSaOC). Olaparib (O) is an option as monotherapy for patients with BRCA1/2 mutations or in combination with bevacizumab (O+B) for Homologous Recombination Deficiency (HRD+) patients. Meanwhile, niraparib (N) is approved irrespective of biomarker status. This study aimed to evaluate the cost-effectiveness of biomarker testing and treatment with PARP inhibitor mTx in PSaOC patients from the perspective of a US payer. Methods: Ten testing and treatment strategies (Table 1) were evaluated, representing common biomarker testing (none, BRCA or HRD) and mTx (O, O+B, N, B) in approved populations. PAOLA-1 trial data were used to build a lifetime horizon partitioned survival model with four health states, including progression-free (PFS), post 1st progression (PP1), post 2nd progression (PP2), and death. PFS was modeled through parametric mixture survival modeling to a landmark survival point at five years. Patients who remain PFS at year five are assumed to be long-term survivors. Time to PP2 and OS was modeled by fitting standard parametric models, and time on treatment data was informed by respective trials (up to 24m for O, 15m for B, treat to progression for N). The hazard ratio (HR) of PFS for O+B versus N (0.57 for HRD+/ITT; 0.46 for BRCA+) and O+B versus O (0.71 for BRCA+) were obtained from matching adjusted indirect comparison (MAIC) between PAOLA1 and PRIMA, and PAOLA1 and SOLO1. The HRs for OS are informed by PFS benefits and published OS data. The incremental cost-effectiveness ratios (ICERs) were calculated. Results: Strategy 2 (S2, no testing, B) had the lowest cost while S10 (HRD testing, O+B for HRD+ and B for HRD-) had the greatest life- years (LYs) and quality-adjusted life-years (QALYs). All of the niraparib strategies were dominated (i.e., had higher cost, lower LY/ QALYs), compared to at least one other strategy (Table 1). When compared to S2, S8 had lower ICERs than S4 ($41,204 per LY and $48,211 per QALY for S8 vs S2). S10 had an ICER of $66,588 per LY and $82,321 per QALY compared to S8. Conclusions: HRD testing followed by O+B for BRCA -/HRD+, O for BRCA+ and B for HRD- (S8) is highly cost-effective, dominating six strategies (all except 2, 4 &10) and having ICERs < $50,000/QALY compared to the least costly strategy (S2). Replacing O with O+B in BRCA+ patients (S10) improves outcomes, with ICER < 100,000/QALY compared to S8. All strategies involving niraparib were dominated by other approaches. An HRD biomarker-guided approach followed with O±B treatment in HRD+ patients provides the greatest LY and QALYs with good economic value. [ABSTRACT FROM AUTHOR]

Objectives: Evolution in the therapeutic landscape and guidelines for advanced ovarian cancer (AOC)—including increased utilization of poly (ADP-ribose) polymerase inhibitors (PARPi) and bevacizumab (BEV)—has resulted in multiple available treatment sequences. Prior studies have compared interventions in specific populations and lines of therapy, but this approximates the downstream impacts of earlier treatment choices. This study assessed the impact of adding BEV to platinum-based chemotherapy (PBC) over multiple treatment lines in frontline (1L) induction and alongside olaparib (OLAP) in 1L maintenance (per the PAOLA-1 trial), offering a complete picture of the incremental clinical value of BEV and OLAP. Methods: A discrete event simulation model was developed to simulate overall survival (OS) and intermediate clinical outcomes (e.g., time to IL/second-line (2L) treatment discontinuation, progression, and/or death; response to 1L/2L induction; platinum sensitivity) based on patient characteristics and treatment history, explicitly tracking events experienced by initially identical patient cohorts progressing through multiple treatment lines. Electronic medical record data from Tempus were used to inform patient characteristics (age at diagnosis, age, race, stage at diagnosis, among others) and derive predictive equations for two 1L reference pathways: PBC followed by no maintenance and PBC + BEV followed by BEV. In 2L, both sequences administered PBC or non-PBC (if platinum-resistant), with or without BEV, followed by maintenance consisting of OLAP, BEV, or no maintenance, depending on outcomes in 1L and treatment history. After 2L, patients received the best supportive care. Hazard ratios from published trials of OLAP and/or BEV were applied to progression-free survival, and OS was estimated from the predictive risk equations to capture other sequences. Results: Results for all sequences in the model are presented in Table 1. Patients receiving PBC and no maintenance in frontline (S0) accrued 4.0 life-years (LYs) on average. Treating a subset of patients with BRCA mutations (30% as per PAOLA-1) with OLAP maintenance and the remaining patients with no maintenance (S1) resulted in 0.3 incremental LYs versus S0 (total: 4.3 LYs). Treating all patients with PBC + BEV followed by BEV (S2) added 1.0 LYs versus S1 (total: 5.2 LYs). Adding OLAP maintenance to S2 for patients with tumors positive for homologous recombination deficiency (HRD) (S3; 48%, as per PAOLA-1), with HRD negative patients receiving BEV only maintenance, contributed another 0.7 LYs versus S2 (total: 5.9 LYs). Results were robust to variability in treatment effects, hazard ratios, and treatment utilization assumptions. Conclusions: Results reflect a combination of the independent impacts of BEV and OLAP in 1L on OS and their influence on the likelihood of response to 1L induction and platinum sensitivity, both of which are linked to improved patient outcomes. Treatment sequences, adding both BEV and OLAP during 1L, improved intermediate outcomes and OS compared to other sequences for AOC treatment. [ABSTRACT FROM AUTHOR]