From the Journals

PARP inhibitors not cost effective for platinum-resistant ovarian cancer



For patients with platinum-resistant ovarian cancer with BRCA1/2 mutations, third- or fourth-line therapy with poly (ADP-ribose) polymerase (PARP) inhibitors is less cost effective than non–platinum-based chemotherapy or bevacizumab-containing regimens, according to a study published in Gynecologic Oncology.

Compared with PARP inhibitors, intravenous chemotherapy regimens tend to produce lower response rates and shorter median progression-free survival (PFS) in this difficult-to-treat population, according to study author Juliet E. Wolford, MD, of the University of California, Irvine, and colleagues.

PARP inhibitors also have the advantages of oral administration and being well tolerated, the researchers noted. However, they found the expense of PARP inhibitors remains substantially greater per month of PFS, even after accounting for the costs of infusion and toxicity management related to chemotherapy.

“We initially wanted to do this study because we suspected that, when including the costs of infusions and costs of managing toxicities, even though the PARP [inhibitors] were more expensive, they would ultimately be more cost effective because they were well tolerated, oral, and more effective,” Dr. Wolford said in an interview. “Surprisingly, the high costs of the PARP [inhibitors] outweighs any other factors so much so that the costs of receiving infusions or managing the adverse events becomes negligible.”

Dr. Wolford and colleagues developed a model using median PFS and toxicity data from regulatory trials to show patient response, complications (hematologic and nonhematologic), progression, and death.

The researchers compared olaparib, rucaparib, and niraparib individually to non–platinum-based chemotherapy regimens and to regimens containing bevacizumab. The team then estimated the costs of intravenous drugs, infusions, toxicity management, and supportive care, based on 2017 Medicare data.

The cost of non–platinum-based intravenous chemotherapy was $6,412 per quality-adjusted month of PFS, a little more than half the cost of bevacizumab-containing regimens, which was $12,187 per month of PFS.

The cost of PARP inhibitors was much higher: $18,970 per month of PFS for niraparib, $16,637 per month of PFS for rucaparib, and $16,327 per month of PFS for olaparib.

“An interesting, albeit not unexpected, phenomenon we observed in our analyses was that, with the relatively higher response rates and/or duration of response associated with PARP [inhibitor] treatment, higher drug costs are incurred,” Dr. Wolford and colleagues wrote.

“The longer patients remain progression free, the longer they remain on treatment and accumulate treatment-related cost,” the authors wrote, noting that complete responses are rare during recurrence treatment, so patients tend to receive salvage therapy until their disease progresses.

However, Dr. Wolford pointed out that using a model requires making assumptions and that “clinical decisions are not derived from a simulation.

“This type of simulation can facilitate the recognition of the financial burden the use of these novel treatments can place on our patients but, more importantly, can highlight the importance of identifying predictive biomarkers,” she said. “We need to be able to distinguish those patients who will benefit the most from the treatment in order to circumvent patients from experiencing financial toxicity from a therapy they will not derive benefit from.”

In their paper, Dr. Wolford and colleagues also pointed out that the new drugs’ cost-effectiveness could substantially improve with minimal reductions in cost, according to many models.

“Such reductions to improve the affordability of many novel molecules can be achieved through mechanisms which result in more widespread use and increased awareness and accessibility of the targeted agent in clinical practice,” the authors wrote.

Further, this study focused on platinum-resistant patients, who are particularly difficult to treat. Expanding the use of PARP inhibitors or identifying the most clinically meaningful uses of them could improve their cost-effectiveness, including possibly using them earlier in the disease course, the authors noted.

“We know from SOLO-1, PRIMA, and PAOLA-1 studies that using the PARP [inhibitors] as frontline maintenance therapy can have a significant benefit, so likely the trend will be to use the PARP [inhibitors] earlier in the disease course and utilizing the antiangiogenic therapy for recurrences when patients begin to develop platinum resistance,” Dr. Wolford said. “It is important to note, however, that, for the frontline trials, we only have PFS data, as the overall survival data is not yet mature.”

The high current costs of PARP inhibitors also follow a common trend with new oncologic agents, Dr. Wolford noted. “When they are first introduced, the high costs are reflective of the high developmental costs. As use of the novel therapies becomes more pervasive, with the approval of additional indications, the costs will eventually decrease over time.”

Dr. Wolford and colleagues did not report any external funding for this study. Some authors disclosed relationships with a range of pharmaceutical, device, and cancer-related businesses.

SOURCE: Wolford JE et al. Gynecol Oncol. 2020 Mar 13. doi: 10.1016/j.ygyno.2020.02.030.

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