Boston, Mass., August 30, 2017 – The Institute for Clinical and Economic Review (ICER) has released an Evidence Report assessing the comparative clinical effectiveness and value of three poly (ADP-ribose) polymerase (PARP) inhibitors for treatment of advanced ovarian cancer: olaparib (Lynparza™, AstraZeneca), niraprib (Zejula™, Tesaro, Inc.), and rucaparib (Rubraca®, Clovis Oncology).  The report reviews evidence on the three drugs for treatment of recurrent, breast cancer (BRCA) gene-mutated ovarian cancer as well as for maintenance therapy in women with recurrent disease who have previously responded to platinum-based chemotherapy (“platinum-sensitive” disease).

This Evidence Report will be the subject of an upcoming public meeting of the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) in St. Louis, MO on September 14, 2017.

“PARP inhibitors have the potential to improve upon existing treatment paradigms for women who currently have limited therapeutic options,” noted Dan Ollendorf, PhD, ICER’s Chief Scientific Officer. “Differences in study design and measurement prevented us from making any explicit comparisons between these drugs, however.  And, with the exception of olaparib for patients with recurrent BRCA-mutated disease, the prices of the agents are out of alignment with the potential benefit they provide to patients over alternative treatments.  During our public meeting in September, ICER intends to facilitate a multi-stakeholder conversation focused on policies that can ensure sustainable access to these drugs by patients who might benefit.”

A draft version of this report was previously open for a four-week public comment period.  The updated Evidence Report reflects changes made based on comments received from patient groups, clinicians, the manufacturers of the drugs, and other stakeholders.

Key Report Findings

For patients with recurrent, BRCA-mutated disease, evidence on the net health benefit of both olaparib and rucaparib was considered promising but inconclusive as there are currently no studies examining their performance against an alternative treatment.  Evidence was judged insufficient for niraparib, as the results of an ongoing trial are not yet available.  For maintenance therapy in patients with platinum-sensitive disease, evidence provided high certainty of at least a comparable net health benefit for olaparib and niraparib when compared to placebo (observation only without active treatment), but was insufficient for rucaparib, as full data from the trial of rucaparib in this indication are not yet available.

While substantial uncertainty remains about the clinical impact of PARP inhibitors, it is also important to consider benefits of therapies that may not be adequately captured in the clinical literature. Mortality rates in ovarian cancer are high, and there have not been significant advances in treatment in over 20 years.  PARP inhibitors offer a novel mechanism of action and represent an additional tool for the treatment armamentarium, and because they can be taken orally, offer added convenience for patients.

ICER’s cost-effectiveness calculations found that use of olaparib in recurrent, BRCA-mutated ovarian cancer met commonly cited cost-effectiveness thresholds of $50,000-$150,000 per quality-adjusted life year (QALY) gained; in all other analyses with available data (rucaparib for BRCA-mutated disease, olaparib and niraparib for maintenance therapy), PARP inhibitor therapy greatly exceeded cost-effectiveness thresholds. To align prices of the drugs that did not meet cost-effectiveness thresholds with the benefit they provide to patients, discounts from wholesale acquisition cost ranging from 50-74% would be needed.

The Evidence Report, as well as accompanying voting questions, all public comments received on the draft report, and ICER’s written response to comments, are available on the ICER website.

During the September public meeting, the Midwest CEPAC, one of ICER’s three independent appraisal committees, will vote on key questions raised in the report, and a policy roundtable of experts will discuss recommendations to apply the evidence to policy and practice.  During the meeting, pre-registered stakeholders will provide brief oral comments on the report and its findings.  Requests to make an oral comment were accepted during the public comment period on the Draft Evidence Report and are now closed.

Registration for the in-person meeting is open here.  Registration for a live webcast of the meeting is open here.