“Many of you have probably been in the same situation that I have, where I have a patient in front of me and have to say, ‘Yes, this would be a good drug for you, but you need to fail a couple more lines of chemotherapy first,’ ” she said. “And we all know that later in the disease course, GI symptoms become more prominent and an oral drug may not be tolerated, so we might lose the opportunity to treat these patients with these drugs.”
Therefore, the field should address some key unanswered questions about PARP inhibitor therapy, according to Dr. Swisher: “Really, what is the best time point for using it – is it at maintenance, or is it at the time of relapse? And if we use it as maintenance, is it in the primary setting or the recurrent setting?” she elaborated.
She noted that women with somatic BRCA mutations as opposed to germline ones seem to benefit similarly from olaparib, but as insurance companies in the United States often resist covering tumor testing, this subset of women is often missed. “Predictors of response and resistance other than BRCA mutations are needed,” she added.
Models suggest maintenance therapy is not cost-effective
In the third study, investigators led by Dr. Haller J. Smith, a resident in obstetrics and gynecology at the University of Alabama, Birmingham, constructed models to assess the cost-effectiveness of olaparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer.
Susan London/Frontline Medical News
Dr. Haller Smith
They used as a target population 5,549 women who had a complete response to primary therapy, experienced a recurrence, and then had at least a partial response to second-line chemotherapy. Analyses assumed a germline BRCA mutation prevalence of 20%.
In the model, patients received six cycles of chemotherapy, followed by either observation or olaparib maintenance therapy. The cost of olaparib was set at $7,000 per month, while the cost of observation was based on national guidelines and Medicare reimbursement rates. “The cost of adverse events was not included in the model as the majority of these in the phase II trial were grade 1 or 2,” Dr. Smith noted.
Results of the base case analysis showed that among patients with a BRCA mutation, the incremental cost-effectiveness ratio (ICER) for olaparib relative to observation was $135,672 per progression-free life-year saved – more than double the $50,000 threshold the investigators considered to be cost-effective, Dr. Smith reported. Among patients with wild type for BRCA, the ICER was sharply higher, at $315,840.
Sensitivity analyses showed that olaparib therapy was still not cost-effective when the prevalence of BRCA mutations and progression-free survival were varied. But the ICER fell to $97,404 when the cost of the drug was reduced to $5,000 and fell to $49,584 when it was reduced to $2,500.
“In order to achieve an ICER of less than $50,000, the cost of olaparib would have to be $2,500 or less per month,” Dr. Smith said. However, “in the era of molecular targeted therapies, an ICER of less than $100,000 would be considered by many to be cost-effective,” she acknowledged.
“While PARP inhibitors and other molecular targeted therapies represent exciting new therapeutic options for our patients, the costs associated with these drugs remain a significant concern. As health care costs continue to increase, cost-effectiveness studies are likely to become a more important part of the drug development and approval process,” she concluded.