Increased Risk for Death Prompts Withdrawal of Three PARPi Indications for Ovarian Cancer 

Sharon Worcester, MA

September 23, 2022

Multiple drug companies have recently withdrawn their respective PARP inhibitors for heavily pretreated ovarian cancer patients, citing data showing an increased risk for death.

In a September 14 letter to healthcare professionals, GlaxoSmithKline (GSK) announced the voluntary withdrawal of niraparib (Zejula) for fourth-line treatment in adults with advanced ovarian, fallopian tube, or primary peritoneal cancer associated with homologous recombination deficiency-positive status.

In an August 26 letter, AstraZeneca and Merck similarly voluntarily withdrew olaparib (Lynparza) for fourth-line treatment in adult patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer.

And this past June, Clovis Oncology withdrew its US indication of rucaparib (Rubraca) for third-line or greater treatment of patients with BRCA-mutated ovarian cancer, announcing the decision in a securities filing.

Each company emphasized that these withdrawals do not affect other indications for the drugs.

The Withdrawals

GSK said its withdrawal of niraparib "was made in consultation" with the US Food and Drug Administration (FDA) and was "based on a totality of information from PARP inhibitors in the late line treatment setting in ovarian cancer."

In the company's withdrawal letter, GSK explained that a "potential detrimental effect on overall survival was observed with other (non-GSK) PARP inhibitors in two independent randomized, active-controlled clinical trials conducted in a BRCA mutant 3L+ advanced ovarian cancer population."

AstraZeneca and Merck, which jointly developed olaparib, cited "a potential detrimental effect on overall survival" compared with the chemotherapy control arm in a subgroup analysis of the phase 3 SOLO3 study.

Olaparib was approved for its fourth-line indication based on findings from the single-arm Study 42, which showed improved objective response and duration of response with the agent compared with chemotherapy. However, SOLO3, an open-label, randomized, controlled study requested by the FDA to further assess olaparib's efficacy and safety, found a 33% increased risk for death in those treated with a PARP inhibitor.

And finally, Clovis Oncology's withdrawal of rucaparib was based on overall survival data in the primary efficacy populations from the pivotal double-blind ARIEL4 clinical trial, which ultimately showed a 31.3% risk for death compared with chemotherapy in this population, particularly in patients with platinum-resistant tumors.

Adverse events associated with these or other drugs should be reported to the drug maker and/or the FDA via the online MedWatch reporting system.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at or on Twitter: @SW_MedReporter.

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