Indications have been withdrawn for several PARP inhibitors in the US for heavily pretreated patients with BRCA-mutated ovarian cancer following ‘detrimental’ survival results in two recent trials.
The voluntary withdrawals apply to late-line treatment indications for olaparib, niraparib, and rucaparib, but do not affect other indications for PARP inhibitor maintenance treatment in ovarian and other cancers.
In August AstraZeneca wrote to healthcare professionals to advise that it was voluntary withdrawing the indication for olaparib for treatment of patients with BRCA mutation advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.
The company said the decision was based on a subgroup analysis of the phase 3 SOLO3 study, which showed “a potential detrimental effect on overall survival” for olaparib compared with the chemotherapy control arm.
The study found a 33% increased risk for death in those treated with a PARP inhibitor compared to chemotherapy (median OS 29.9 vs 39.4 months).
The company advised physicians to share the information with patients being treated with this indication ‘so they can make an informed decision regarding their ongoing care”.
Similarly in June the third line indication for another PARP inhibitor, rucaparib, was withdrawn based on unfavourable overall survival data from the double-blind ARIEL4 clinical trial, which showed a 31.3% risk for death compared with chemotherapy in patients with high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer.
And in September, GSK announced voluntary withdrawal for its PARP inhibitor niraparib for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status.
The company said there had been no new safety data for niraparib and the decision was made in consultation with the FDA based on “a totality of information from PARP inhibitors in the late line treatment setting in ovarian cancer.”
“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,” the announcement said.
It stressed the withdrawal did not apply to other indications such as maintenance treatment of patients who are in a complete or partial response to first-line platinum-based chemotherapy, or patients with recurrent cancer who are in a complete or partial response to platinum-based chemotherapy.
In response to the new trial data, ASCO has also revised its guidance for the use of PARP inhibitor therapy in the management of ovarian cancer.
The rapid recommendation update notes the recent regulatory changes for PARP inhibitor monotherapy for the treatment of recurrent platinum-sensitive epithelial ovarian cancer.
While PARP inhibitor monotherapy is still recommended for newly diagnosed ovarian cancer and as maintenance therapy, it “should not be routinely offered to patients for the treatment of recurrent platinum sensitive epithelial ovarian cancer,” the guidance states.
“Evidence on PARPi use in this setting is evolving and data are continuing to emerge. Any decision to proceed with PARPi treatment in select populations (BRCA mutation, No prior PARPi use, Platinum Sensitive, Advanced Lines of Treatment) should be based on individualized patient and provider assessment of risks, benefits, and preferences,” it advises.
In a statement, GSK noted that in November the FDA is to discuss overall survival (OS) data from its ENGOT-OV16/NOVA phase III clinical trial of niraparib for the maintenance treatment of women with platinum-sensitive recurrent ovarian cancer.
“We believe PARP inhibitors, including (niraparib), are important options for the maintenance treatment of patients with recurrent ovarian cancer, across all biomarker subgroups, who are in complete or partial response to platinum-based chemotherapy. We look forward to continuing our ongoing discussions with the FDA,” said Hesham Abdullah, SVP, Global Head of Oncology Development, GSK.