PARP Inhibitors Show Promise in Patients with Recurrent Ovarian Cancer

Maintenance therapy with a poly (ADP ribose) polymerase (PARP) inhibitor demonstrated benefits including progression-free survival for those with high-grade, recurrent, platinum-sensitive ovarian cancer, according to data published in Cancer.

The benefit from this particular maintenance therapy was prominent in patients with the BRCA mutation, according to the study. BRCA mutations can be considered either germline (passed from parent to offspring) or somatic (DNA alteration after conception that is not passed on to children).

Evaluating four trials from a database, researchers sought to compare treatment with PARP inhibitors or placebo. From these four trials, 972 patients received PARP inhibitors and 530 patients received placebo. In particular, for patients treated with PARP inhibitors, 31% received Lynparza (olaparib), 35% received Zejula (niraparib) and 34% received Rubraca (rucaparib).

Benefit with PARP inhibitors were observed in patients with a germline BRCA1 mutation (471 patients, in those with a germline BRCA2 mutation (236 patients) and in patients with a somatic BRCA mutation (123 patients). Treatment effects were similar in patients with either germline or somatic BRCA mutations.

Researchers also assessed 309 patients with wild-type BRCA (a gene in its natural, unchanged form) homologous recombinant-deficient tumors, meaning that tumors have lost the ability to repair a particular DNA break, which can increase a patient’s risk of damaging DNA through certain drugs like PARP inhibitors and platinum-based agents. This analysis also included 346 patients with wild-type BRCA homologous recombinant-proficient tumors. Patients with homologous recombinant-deficient tumors had a greater treatment effect with PARP inhibitors compared with those with homologous recombinant-proficient tumors.

The benefit from PARP inhibitors did not differ by response after recent chemotherapy, age and prior treatment with Avastin (bevacizumab).

The study had several limitations including the authors’ assumption that PARP inhibitors including Lynparza, Zejula and Rubraca, had the same therapeutic efficacy across all of the trials. Authors also note the analysis was not based on overall survival.

“Most importantly, our current analysis is not based on (the overall survival) outcome, which may be considered a more clinically relevant end point for this patient population with an incurable cancer,” the study authors wrote.

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