Chicago, IL—Poly (ADP-ribose) polymerase (PARP) inhibitor maintenance therapy with olaparib (Lynparza) for relapsed, platinum-sensitive ovarian cancer would meet conventional standards of cost-effectiveness only if the drug price decreased by ≥66%, according to a modeling study.
Assuming a $7000 monthly cost for olaparib would lead to an incremental cost-effectiveness ratio (ICER) of $135,672 if treatment were limited to patients with BRCA1/BRCA2 mutations. Using the drug as maintenance for BRCA wild-type tumors would drive the ICER to $315,840.
PARP inhibitor maintenance with olaparib would far exceed the conventional $50,000 willingness-to-pay threshold and even the more generous $100,000 threshold used in some recent discussions of cost-effectiveness, said Haller J. Smith, MD, of the University of Alabama, Birmingham, at the 2015 Society of Gynecologic Oncology annual meeting.
“At a cost of $7000, olaparib is not cost-effective, regardless of the BRCA status,” said Dr Smith. “Restricting olaparib use to patients with BRCA1/2 mutations decreased costs, but to achieve an acceptable ICER, the cost of olaparib must be $2500 or less.”
In December 2014, the FDA approved olaparib for the treatment of patients with relapsed, platinum-sensitive ovarian cancer with BRCA mutation who were previously treated with ≥3 lines of therapy.
In approving the drug, the FDA overruled the Oncologic Drugs Advisory Committee (ODAC) recommendation, which voted against approval. ODAC members had expressed concern about an excess of hematologic malignancies and an approval request based on a phase 2 trial subgroup analysis (of patients with BRCA mutations) showing improved progression-free survival (PFS) but not overall survival.
However, the FDA did stipulate that the approval is contingent on the outcome of 2 ongoing phase 3 trials of olaparib maintenance in relapsed, BRCA-mutated ovarian cancer. PFS is the primary end point in both trials, and results are expected later this year.
Dr Smith and colleagues performed a cost-effectiveness analysis, using a model based on 6 cycles of carboplatin plus paclitaxel chemotherapy, followed by olaparib maintenance therapy.
Cost was defined as the total cost of the strategy, and effectiveness as the improvement in PFS arising from the strategy. The ICER represented the cost per progression-free life-year saved.
Cost components of the treatment strategy consisted of $121.67 per cycle of paclitaxel, $51.81 per cycle for carboplatin, $386.22 for premedication, $100.73 for a level 4 office visit, $112.20 for CA-125 assessment, $312.37 for a chest computed tomography (CT), $482.89 for CT of the abdomen and pelvis, and $7000 for a 30-day supply of olaparib.
The cost of the PARP inhibitor was derived from costs of similar types of drugs. The remaining drug costs were based on 2014 wholesale acquisition costs.
The model’s assumptions included 1110 patients with recurrent, platinum-sensitive ovarian cancer with BRCA mutations who were treated each year. Observation would cost $5.5 million and result in a PFS of 4.3 months. Olaparib maintenance for the same patients would result in a PFS of 11.2 months at a cost of $91.3 million, which translated into an ICER of $135,672 per progression-free life-year saved.
An analysis of patients with BRCA wild-type tumors showed that an estimated 4439 patients would be treated at a cost of $22.1 million and result in a PFS of 5.5 months. Olaparib maintenance therapy would cost $244.1 million and yield a PFS of 7.4 months.
Sensitivity analysis showed that if BRCA1 or BRCA2 mutations accounted for 10% (instead of 20%) of patients with recurrent, platinum-sensitive ovarian cancer, the cost of the olaparib strategy would decrease by half, to $46.1 million.
The analysis showed that the greatest cost impact would come from a reduction in the estimated cost of olaparib. If the price of a 30-day supply were $5000, the 11.2-month PFS would be associated with an ICER of $97,404 per progression-free life-year saved, decreasing to $49,584 per progression-free life-year saved if the price of the PARP inhibitor were $2500.