Cost-effectiveness analysis comparing “PARP inhibitors-for-all” to the biomarker-directed use of PARP inhibitor maintenance therapy for newly diagnosed advanced stage ovarian cancer

Abstract

Objectives.

Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a “PARPi-for-all” to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy.

Methods.

The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained.

Results.

PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance.

Conclusions.

This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced.

1. Introduction

Surgical cytoreduction accompanied by platinum-based chemotherapy is the standard of care for treatment of advanced stage ovarian cancer [1,2]. Despite surgery and chemotherapy, the five year survival of these patients remains at 29–48% [3–5]. However, with the advent of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi), the opportunity to exploit the molecular biology of some ovarian cancers has proven promising.

The first clinical reports of PARP inhibitors were published in 2009 [6]. Based on the “synthetic lethality” of PARP inhibition in the presence of a BRCA mutation or homologous recombination deficiency (HRD) [7], initial clinical trials demonstrated the efficacy of PARP inhibition in patients with known germline or somatic BRCA 1/2 mutations or HRD [8–13]. More recently, three randomized trials (VELIA, PRIMA, and PAOLA-1) have evaluated the role of frontline PARP inhibitor maintenance therapy for all, including patients with intact BRCA genes and intact homologous recombination repair (HRR) mechanisms (henceforth referred to as the ‘biomarker negative’ cohort) [14–16]. Based on a significant progression free survival (PFS) advantage in the intent-to-treat cohorts of all 3 trials, a biomarker blind “PARPi-for-all” treatment strategy may have a role in the management of patients with newly diagnosed advanced stage ovarian cancer. However, this approach overlooks the fact that the observed PFS benefit was driven largely by trial participants with BRCA mutations or other HRD mutations (the biomarker positive cohort), with minimal to no PFS benefit observed in biomarker negative trial participants.

As healthcare spending in the United States continues to rise, caution is advisable when adopting costly new therapies without strong evidence that benefits outweigh cost [17]. In light of the recent trials suggesting the benefit of a PARPi-for-all upfront primary maintenance treatment strategy, we seek to question whether this reflects a sensible value-based approach to the care of women with newly diagnosed advanced stage ovarian cancer. Previous cost-effectiveness analyses have suggested that widespread use of PARPi therapy in the recurrence setting is not cost-effective [18,19]. Here, we present an analysis assessing the cost-effectiveness of PARP inhibitor maintenance therapy for all compared to a biomarker-directed PARPi maintenance strategy for patients with newly diagnosed advanced stage ovarian cancer. Our primary objective was to determine the degree of PFS improvement that PARP inhibitor maintenance therapy would need to provide in the biomarker negative population to make a PARPi-for-all strategy potentially cost-effective.

2. Methods

Three decision models were designed to simulate and compare the cost-effectiveness of two PARP inhibitor maintenance therapy strategies for women with newly diagnosed advanced stage ovarian cancer who have completed primary treatment with surgery and chemotherapy: (1) a biomarker-blind PARPi-for-all maintenance treatment strategy; (2) a biomarker-directed PARPi maintenance treatment strategy reserved for patients with either BRCA germline mutations or those with HRD positive tumors.

2.1. Model description

Modified Markov models were created from a third party payer perspective using TreeAge Pro 2019 software (Williamstown, MA) (Fig. 1). Study design and results reported in accordance with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist [20]. The following mutually exclusive Markov states were included: receiving primary chemotherapy treatment, completed chemotherapy and on surveillance, and post-progression or dead. Modeled patient populations reflected the intent-to-treat populations analyzed in the VELIA, PRIMA, and PAOLA-1 trials [14–16]. From the VELIA trial, the experimental arm receiving chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout) and the control arm receiving chemotherapy alone were modeled; the cohort not receiving maintenance veliparib was excluded from the analysis. Patients could receive maintenance veliparib up until disease progression or for a maximum thirty 21-day cycles. For PAOLA-1, chemotherapy including bevacizumab followed by maintenance with olaparib and bevacizumab was evaluated. The control arm included patients receiving chemotherapy and bevacizumab followed by maintenance bevacizumab. Patients were assumed to receive olaparib and bevacizumab maintenance until disease progression or for a maximum of 24 months. Lastly, the PRIMA trial consisted of standard chemotherapy followed by niraparib maintenance and a control arm receiving chemotherapy alone. Patients were assumed to receive niraparib maintenance until disease progression or a maximum of 36 months. The biomarker-directed approach was modeled to provide frontline maintenance PARP inhibitors only to patients with HRD, including those with germline or somatic BRCA mutations. All three trials required assessment of the presence of a germline BRCA mutation and tumor HRD status. An HRD score of 42 or high indicated a positive test in PAOLA-1 and PRIMA. VELIA used a lower cut off score of 33 or higher for inclusion in the HRD cohort. The effectiveness outcome of the models was progression free survival (PFS), and cost-effectiveness was reported as the incremental cost-effectiveness ratio (ICER) in US dollars per quality-adjusted progression-free life year (QA-PFY) gained. QA-PFYs have been described in other cost-effectiveness studies [21–25] and were used instead of quality-adjusted life years because of the absence of published overall survival data. The time horizon for analysis was the total duration of PFS reported in each of the frontline maintenance PARP inhibitor trials (VELIA: 44 months, PRIMA: 28 months, PAOLA-1: 45 months). Incremental cost-effectiveness ratios (ICERs) were calculated in 2018 US dollars per quality-adjusted progression-free year (QA-PFY). Costs and outcomes were discounted at 3% annually [26]. Sensitivity analyses were performed to account for uncertainty in assumptions and inputs to the model. The models were run as Monte Carlo probabilistic analysis using 1000 samples from each modeled distribution. An ICER of $150,000/QA-PFY was used as a surrogate for the commonly cited upper limit of possible societal willingness to pay thresholds of $150,000/QALY [19,25,27]. Key assumptions for construction of the model are listed below.

Fig. 1.

Decision tree with PRIMA model node expanded to reveal entire subtree.

2.2. Survival estimates

We modeled PFS in the absence of PARPi maintenance therapy in defined genetic cohorts (germline or somatic BRCA mutation, HRD, wild-type BRCA/intact HRR) of patients with advanced stage ovarian cancer using published survival curves of patients randomized to placebo in each of the three frontline PARPi maintenance trials [14–16]. To model a representative cohort of patients with advanced stage ovarian cancer, the distribution into each of these genetic cohorts was based on the sequencing data obtained from the Cancer Genome Atlas (TGCA) [28] (Table 1). In TCGA, 20% of patients were identified as having either somatic or germline BRCA mutations and an additional 29% of patients were found to have other homologous recombination defects. To simulate PFS improvements associated with PARPi maintenance, we applied biomarker-specific hazard ratios derived from the published data (Table S1). Survival data from the three trials was modeled from the published Kaplan-Meier curves as follows: the PFS data in the control arms were used estimate raw survival data using the method of Hoyle and Hensley [29] and modeled as beta distributions at 6 month intervals. The hazard ratios associated with experimental arms were modeled using normal distributions to incorporation their confidence intervals [14–16].

Table 1.

Model Inputs

Clinical variable	Estimate	Range	Source
Distribution of genetic cohorts
Probability of homologous recombination deficiency tumor	0.49	0.3–0.7	28
Probability of BRCA mutation	0.20	0.15–0.45
Cost estimate	Cost (2018 US Dollars)	Range	CPT Code/source
Olaparib	$15,159 (30-day supply)	$100–18,000	Duke University Pharmacy
Niraparib	$18,070 (30-day supply)	$100–18,000	Duke University Pharmacy
Veliparib	$13,000 (30-day supply)	$100–18,000	Duke University Pharmacy
Bevacizumab	$3821 per 16 mL vial (25 mg/mL)	$100–13,000	Duke University Pharmacy
Carboplatin/Paclitaxel	$311 per cycle		Duke University Pharmacy
Grade 3–4 adverse hematologic events	$7729 per year		30
HRD testing	$4040		Myriad Genetics

Clinical and cost model inputs. HRD = homologous recombination deficiency; Biomarker negative = intact homologous recombination repair; PFS = progression free survival; PARPi = poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors.

2.3. Costs and clinical assumptions

Costs incorporated into the models included those of PARP inhibitors, HRD testing, and of treating grade 3–4 hematologic toxicities (see Table 1) [30]. The costs of olaparib ($15,159, 30-day supply), niraparib ($18,070, 30-day supply), and bevacizumab ($3821 per 16 mL vial) were obtained from the wholesale prices paid by the pharmacy at the authors’ institution. Veliparib is currently not FDA approved for any indication; we therefore assumed a cost of $13,000 for a one month supply of veliparib as a low end estimate of what the drug will cost. The weighted cost of treatment for each drug was developed based on published data regarding dose reductions and discontinuations (supplemental Table S1). All costs were adjusted to represent 2018 U.S. dollars using Tom’s Inflation Calculator [31]. The cost of germline BRCA mutation testing was not included in the model, as the current standard of care is for all patients with epithelial ovarian cancer to undergo germline genetic testing. All patients in the biomarker-directed treatment strategy were assumed to undergo HRD testing. The cost of HRD testing was obtained directly from the testing company.

2.4. Sensitivity analysis

The base case model was run as a Monte Carlo simulation of 1000 trials to assign confidence intervals around the model outcomes. We additionally performed multiple one-way sensitivity analyses on the following key variables to assess variation in costs: Hazard ratio representing the PFS improvement with PARPi for biomarker negative patients, proportion of patients with HRD or BRCA mutations, cost of PARP inhibitors. The cost of bevacizumab was varied in the PAOLA-1 model (Table 1). We performed an additional two-way sensitivity analysis in which we simultaneously varied the PFS hazard ratio of the biomarker negative cohort and the cost of PARP inhibitors.

3. Results

3.1. Cost

The mean cost per patient of the PARPi-for-all strategy was $166,269 in the PRIMA model, $286,715 in the VELIA model, and $366,506 in the PAOLA-1 model (Table 2). The ranges in cost were dependent on the specifics of each of the three trials modeled including efficacy, timing of initiation of maintenance therapy (with initiation of standard chemotherapy or following completion of chemotherapy), presence of absence of bevacizumab in the baseline regimen, and cost of individual PARP inhibitors. By comparison, the mean cost per patient of a biomarker-directed strategy was $98,188 for PRIMA, $167,334 for VELIA, and $260,671 for PAOLA-1 (Table 2). Therefore, the additional incremental cost of the PARP-for-all strategy is $68,081 in PRIMA model, $119,381 in the VELIA model, and $105,836 in the PAOLA-1 model.

Table 2.

Cost and ICERs by strategy.

Strategya	Cost/Patient ($) by strategy, (95% CI)	ICER ($/QA-PFY)
VELIA-		1,513,495
PARPi-for-all	286,715 (270,241–302,251)
Biomarker-directed	167,334 (156,666–174,025)
PRIMA-		593,250
PARPi-for-all	166,269 (154,396–177,058)
Biomarker-directed	98,188 (88,787–105,544)
PAOLA 1-		3,347,915
PARPi-for-all	366,506 (350,965–379,870)
Biomarker-directed	260,671 (253,015–266,805)

ICER = incremental cost effectiveness ratio; QA-PFY = quality adjusted progression free year.

The bold text in italics represents the strategy by frontline PARPi maintenance trial.

^aPARPi-for-all versus biomarker-directed strategy for the VELIA, PRIMA, PAOLA-1 frontline maintenance trials.

3.2. Cost-effectiveness

The PARPi-for-all frontline maintenance strategy was not cost-effective when compared to a biomarker-directed approach. In the PRIMA model for niraparib maintenance, the ICER for the PARPi-for-all strategy compared to the biomarker-directed strategy was $593,250/QA-PFY. In VELIA for frontline veliparib followed by maintenance, the ICER for the PARPi-for-all strategy compared to the biomarker-directed strategy was $1,512,495/ QA-PFY. In the PAOLA-1 model for bevacizumab plus olaparib maintenance, the ICER for the PARPi-for-all strategy compared to the biomarker-directed strategy was $3,347,915/QA-PFY (Table 2).

3.3. Sensitivity analyses

Several one-way sensitivity analyses were conducted. When we varied the PFS hazard ratio for the biomarker negative cohorts in the PARPi-for-all strategy model, there was no PFS improvement that would make a PARPi-for-all frontline maintenance strategy cost-effective at a threshold of $150,000/QA-PFY. To test whether the proportion of patients whose tumors harbor HRD or BRCA mutations in the modeled population would alter the cost-effectiveness of the PARPi-for-all strategy, we varied the proportion of the HRD/BRCA population in the model from 30%–70%. Within this range, the PARPi-for-all strategy’s ICERs remained well above the estimated willingness to pay threshold of $150,000/QA-PFY. Last, we varied the cost of each PARP inhibitor and of bevacizumab. In the PAOLA-1 model, olaparib would have to cost $560/month or less to be cost-effective. There was no lower cost of bevacizumab that would make PARPi-for-all cost effective, as it was administered to all subjects in that trial. In the PRIMA model, niraparib would have to cost $2962/month or less for the PARPi-for-all strategy to be cost-effective. For comparison, the actual cost of PARP inhibitors is estimated to be $15,159/month for olaparib and $18,070/month for niraparib. At a willingness to pay threshold of $150,000/QA-PFY, there is no cost of veliparib low enough to make a PARPi-for-all treatment strategy cost-effective. The results of the one-way sensitivity analyses are depicted in the tornado diagrams in Fig. 2. The graphic shows the impact of varying individual input on the cost-effectiveness of PARPi-for-all compared to biomarker-directed maintenance. In all three trials, the models’ results are most sensitive to the PFS hazard ratio for the biomarker negative cohort and the cost of the PARP inhibitors.

Fig. 2.

Tornado diagram of the one-way sensitivity analysis indicates that the outcome is most sensitive to variation in the PFS hazard ratio of the biomarker negative cohort and the cost of PARP inhibitor therapy. Red line: Willingness-to-pay threshold of $150,000 QA/PFY; Blue line: Base-case ICER for the individual trial; WTP = willingness to pay; ICER = incremental cost effectiveness ratio; H.R. = hazard ratio.

Two-way sensitivity analyses were performed in which the PFS hazard ratio for the biomarker negative cohort and the cost of the PARP inhibitor were varied simultaneously (Fig. 3). In PAOLA-1, PARPi-for-all could be cost-effective if the PFS hazard ratio for the biomarker negative cohort was less than 0.25 and cost of olaparib was less than $4810/month. In PRIMA, PARP-for all could be cost effective if the PFS hazard ratio for the biomarker negative cohort was less than 0.5 and the cost of niraparib was less than $4295. Compared to the other two trials, there were limited ranges for these same inputs in VELIA that would make the PARPi-for-all cost-effective.

Fig. 3.

Two-way sensitivity analysis. Red area indicates that a biomarker-based strategy is preferred if the willingness-to-pay threshold is $150,000/quality adjusted progression free year (QA-PFY). Blue area indicates that a PARPi-for-all strategy is preferred if the willingness-to-pay threshold is $150,000/ QA-PFY.

4. Discussion

Multiple clinical trials have demonstrated a progression free survival benefit of maintenance PARPi therapies for patients with newly diagnosed ovarian cancer. In these trials, patients with homologous recombination deficient tumors and BRCA mutations derived the greatest PFS benefit. This is similar to the findings of the SOLO-1 trial, where patients with mostly germline BRCA 1 or 2 mutations gained significant PFS benefit with olaparib maintenance [12]. Given the results of SOLO-1, Olaparib was granted FDA approval for frontline maintenance therapy in patients with deleterious germline or somatic BRCA-mutated advanced ovarian cancer [32]. Recently, niraparib was approved for frontline maintenance use in all patients regardless of their tumor HRD or BRCA mutation status following the publication of the PRIMA trial [33]. In the current study, we demonstrate that adopting a PARPi-for-all maintenance strategy in patients with newly diagnosed advanced stage ovarian cancer is not cost-effective when compared to a targeted, biomarker-directed approach. With evidence that efforts to rein in health care spending in the United States are failing [34], we should examine new therapies and technologies closely to ensure that they represent value-based care strategies and keep the interests of both patients and payers in mind. Our results indicate that a biomarker-directed strategy provides higher health care value when compared with a PARPi-for-all strategy.

The ICERs for the PARPi-for-all strategy compared to a biomarker directed approach were $3,347,915/QA-PFY, $593,250/QA-PFY, and $1,512,495/QA-PFY for olaparib, niraparib, and veliparib respectively, when compared to a biomarker-directed approach. These estimates, while not expressed using QALYs due to the lack of overall survival data, are all in a range that would be difficult to consider cost-effective. The wide variation in ICERs between the trials is driven by the timing of the use of PARP inhibitors in relation to adjuvant chemotherapy and the length of clinical follow up in the individual study. In VELIA, patients received veliparib both in combination with chemotherapy and as maintenance after completion of upfront chemotherapy. In PAOLA-1, bevacizumab was given in combination with chemotherapy and maintenance olaparib which added significantly to overall treatment costs but did not affect the ICER. In one way sensitivity analyses, the cost of PARP inhibitors would have to be reduced by 96% to $560/month for olaparib and by 83% to $2962/month for niraparib to make a PARPi-for-all strategy cost-effective; no lowering of veliparib’s cost would make a PARPi-for-all strategy cost-effective (See Supplemental Table 2). This is consistent with previously published cost-effectiveness data for PARPi maintenance in the recurrent setting where niraparib and olaparib pricing would have to be discounted up to 90% to meet threshold of $150,000/QALY in this setting [35]. This was likely driven by a combination of the additional cost of veliparib during the upfront treatment phase, the lack of demonstrable PFS benefit in the biomarker negative cohort, and the shortened time horizon.

The PRIMA, VELIA, and PAOLA-1 trials have each demonstrated an approximately 6 month PFS benefit in the intent-to-treat populations of a maintenance PARPi-for-all treatment approach for patients with newly diagnosed advanced stage ovarian cancer, with overall hazard ratios ranging from 0.59–0.68 [14–16]. In these three trials, the significant PFS benefit observed appears to be driven largely by the biomarker positive patients where the PFS hazard ratios were lower (HR 0.33–0.57). Conversely, biomarker-negative patients failed to gain any significant PFS benefit in VELIA and PAOLA-1, while only achieving a 2.7 month survival benefit in PRIMA (HR 0.68, CI 0.49–0.94). Studies of PARPi maintenance in the recurrent setting have similarly shown that a PARPi-for-all strategy is not cost-effective [18,19,25]. One potential approach to improving relative cost-effectiveness is value-based pricing of expensive new oncology therapies, in which the price would be considerably lower in biomarker negative patients who derive less benefit. Such pricing could be guided by health economic analyses such as those presented in this paper. This concept has been endorsed by American Society of Clinical Oncology (ASCO) and is worthy of further consideration [36,37].

The efficacy data in biomarker negative cohorts in the PRIMA, VELIA, and PAOLA-1 trials in conjunction with the present study provide a compelling argument for the consideration of adopting a more nuanced approach to maintenance PARPi therapy for patients with newly diagnosed ovarian cancer. Broadly speaking, a biomarker-directed approach that preferentially provides maintenance PARPi therapy for biomarker positive patients might represent a more sensible value-based treatment model that exploits our understanding of ovarian cancer biology. This approach would not necessarily preclude biomarker negative patients from receiving PARPi maintenance therapy but would encourage oncology providers to have individualized discussions with patients about costs, side effects, and expected benefits of their cancer treatment. Discussions regarding expected benefit are especially important, as providers should be offering therapies that are likely to provide clinically meaningful results. Additionally, the ASCO guidance statement on the cost of care encourages providers to include patients in conversations about costs of care so that each patient gets high value, high quality care [38]. Financial toxicity due to expensive cancer treatments is a significant cause of distress and even bankruptcy [39].

The clinical meaningfulness of frontline PARPi maintenance therapy in biomarker negative patients should be scrutinized given a reported benefit ranging from 0 to 2.7 months in the PRIMA, VELIA, and PAOLA-1 trials. ASCO conducted working groups that included leading clinicians, policy makers, and patient advocates to help better define clinically meaningful results in breast, pancreas, colon, and lung malignancies and reported an improvement in PFS of 3–5 months as clinically meaningful in these cancers [40]. Similar arguments for establishing clinically meaningful result thresholds in advanced stage ovarian cancer have been made [41–43] and should be kept in mind when implementing costly new therapies. In our group’s recent survey study of the preferences of women with ovarian cancer regarding PARPi maintenance therapy, 78% of participants indicated that they would favor a treatment break over gaining 2 months of PFS with a maintenance therapy that would incur mild nausea, mild fatigue, $50 per month out of pocket cost, and no additional overall survival benefit [44]. While the primary outcome of the frontline maintenance trials was not designed to exclusively pick up a signal in biomarker negative patients, secondary and exploratory analyses do not provide strong evidence that these patients are deriving meaningful benefit from PARP inhibitors.

There are several limitations to our study that warrant mentioning. First, our models were limited to published data which has not matured, substantially shortening the time horizon for analysis. A short-term horizon can influence the value of an intervention and may not capture the actual costs and effects between alternatives in the model. It is feasible that our models terminate prior to reaching a time point that reflects the full clinical benefit in the biomarker negative cohorts. However, given the convergence of the PFS curves, we feel this is unlikely. Second, assumptions are made in our models that might not always be applicable or accurate in all patient populations. For example, the proportion of patients with HRD might vary from one patient population to the next, and while this variability did not influence our model, it certainly might have an impact under circumstances of extremes. Importantly, cost inputs may vary geographically and with time. However, we believe our estimates would be applicable to expected costs in United States. Last, we used QA-PFY as a surrogate for QALY and used an upper willingness-to-pay threshold to also be $150,000/QA-PFY based on the accepted threshold for a QALY. Other studies have similarly used quality adjusted progression free year as a surrogate for a quality adjusted life year, however, it is worth mention that the value of spending money to delay recurrence is debatable if there is ultimately no improvement in overall survival. If long term follow-up of the first line PARP inhibitor maintenance trials ultimately show no gains in either median overall survival or cure rates for any of the studied cohorts, this therapy may be best utilized in the recurrence setting. In this regard, 10–20% of patients who have a complete response to surgery and primary platinum-based chemotherapy never develop recurrent disease. These patients will therefore also not derive any benefit from maintenance PARP inhibitor maintenance therapy, but will nonetheless be subjected to its high cost, side effects and complications. Conversely, the majority of patients who are destined to develop recurrence could receive biomarker-directed PARP inhibitor maintenance after response to second line platinum-based chemotherapy. This could represent the best value-based strategy for use of PARP inhibitor maintenance if these agents do not actually add good quality life years for women with advanced stage ovarian cancer.

This study highlights the very important role that PARPi pricing plays in overall costs for patient with advanced stage ovarian cancer. In 2020, drug prices will continue to soar in the United States with little regulation on how pharmaceutical companies set prices on prescription drugs [45,46]. The Society of Gynecologic Oncology has for some time taken the position that drug pricing should be made a national priority with some suggestions to achieve lower costs for oncology patients including: government negotiation of drug prices, transparency on how pharmaceutical companies set prices, and integration of value-based pricing strategies [47]. Unfortunately, it is unlikely that legislation will be adopted in the near future. This study outlines the complexity of PARPi maintenance therapy and encourages providers to consider a personalized value-based approach when deciding on the appropriateness of maintenance PARPi therapy for patients with newly diagnosed advanced stage ovarian cancer.

HIGHLIGHTS.

• Recent trials demonstrated progression free survival benefit with frontline PARP inhibitor maintenance

• Largest PFS benefit seen in patients with mutant BRCA or HRD

• Universal PARPi frontline maintenance is not cost-effective

• Frontline PARPi maintenance should be reserved for patients with BRCA mutations or homologous recombination deficiency