PARP Inhibitors Least Cost-Effective as Maintenance Therapy in Advanced Ovarian Cancer

August 2018 Vol 11, Special Issue - Value-Based Care
Chase Doyle

Chicago, IL—Poly (ADP ribose) polymerase (PARP) inhibitors are among the new and improved classes of cancer drugs, but their steep costs have become a critical consideration for patients and clinicians. The results of a recent analysis suggest that PARP inhibitors may be the least cost-effective of available maintenance therapies for advanced ovarian cancer. According to data presented at ASCO 2018, to become cost-neutral with anti-VEGF therapy, PARP inhibitors would require at least a 50% reduction in cost.

"High starting costs of PARP inhibitors together with daily dosing and longer median progression-free survival [PFS] associated with germline BRCA mutation carriers make PARP inhibitors the least cost-effective of potential maintenance therapies in advanced ovarian carcinoma," said lead investigator Juliet Elizabeth Wolford, MD, Gynecologic Oncology Fellow, University of California, Irvine. "Assigning scores to healthy utility states to account for toxicology does very little to mitigate the high costs associated with these novel targeted therapies."

Given the high rate of recurrence, several phase 3 randomized clinical trials have studied novel maintenance therapies in women with primary advanced and recurrent ovarian cancer. For this study, Dr Wolford and colleagues compared the cost-effectiveness of actual and potential maintenance strategies in ovarian cancer.

The researchers used clinical trials data on the frequency and severity of adverse events and median PFS for drugs used as maintenance therapy in ovarian cancer, including paclitaxel (Taxol), bevacizumab (Avastin), ni­raparib (Zejula), rucaparib (Rubraca), olaparib (Lynparza), and pembrolizu­mab (Keytruda). Because antiangiogenesis therapy was studied in various patient populations, each study was modeled separately. The costs of germline or somatic BRCA testing and the costs of neuropathy and immune-mediated adverse events, including endocri­nopathies, also factored into the model.

Dr Wolford and colleagues constructed a Markov model of patients with recurrent ovarian cancer who had received chemotherapy. The patients transitioned through response to treatment, hematologic and nonhematologic complications, disease progression, and death. Finally, Medicare data were used to estimate the costs of infusions and toxicities.

Maintenance Therapy with Paclitaxel Most Cost-Effective

Maintenance paclitaxel therapy was the most cost-effective agent, at $1329 monthly for improved PFS, whereas PARP inhibitors cost nearly $30,000 monthly for improved PFS.

"With PARP inhibitors, cost is incurred daily based on the oral drug intake schedule, and the trials have shown that patients with germline BRCA mutations tend to have a more favorable prognosis," Dr Wolford said. "In other words, BRCA-deficient patients incur more costs, because they typically live longer progression free and therefore receive more drug."

Ultimately, the cost of the PARP inhibitors before disease progression was approximately 22.5 times more than paclitaxel, 7.5 times more than pembrolizumab, and 3 times more than bevacizumab.

"Because pembrolizumab is only administered once per month, even with a low PFS, when compared to each of the PARP inhibitors in the BRCA-deficient populations, the incremental cost-effectiveness ratios looked relatively cost-­effective," said Dr Wolford, adding that assigning health scores to account for toxicology does very little to mitigate the high costs associated with these novel therapies.

Further analysis showed that the PARP inhibitor niraparib would require a 68% reduction in costs to be cost-neutral with bevacizumab. For pembrolizu­mab to be cost-neutral versus the same anti-VEGF therapy, the median PFS would need to increase from 1.9 months to at least 5 to 8 months. Despite these findings, however, Dr Wolford emphasized that mature overall survival data are still lacking for the PARP inhibitors and will need to be modeled again when those are available. Similarly, immuno-­oncology trials in ovarian cancer will start reporting in the next 1 to 2 years.

To make these novel drugs more cost-effective, several strategies can be used, said Dr Wolford, including identifying lower dosages that do not compromise efficacy, using the drugs earlier in the disease course, expanding the drug indication to include other tumor types, and the development of active and tolerable generics and/or biosimilars.

"When considering economic toxicity, the current trend to study novel combinations is problematic," Dr Wolford said. "The elephant in the room is the absence of validated predictive biomarkers through which unnecessary toxicity and costs can be potentially mitigated."

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