ESMO 2019: Dr. Mirza on Important Trials with PARP Inhibitors in Ovarian Cancer

Mansoor Raza Mirza, MD, chief oncologist, Department of Oncology in Rigshospitalet, Copenhagen University Hospital, discusses data presented with PARP inhibitors in ovarian cancer at the 2019 ESMO Congress.

PARP inhibitors have become standard of care as frontline maintenance therapy in ovarian cancer, says Mirza. Data from 3 positive trials have shown the benefit of using PARP inhibitors in this new paradigm, he says.

Data from the phase III PAOLA-1 trial showed that frontline maintenance therapy with the combination of olaparib (Lynparza) and bevacizumab (Avastin) improved progression-free survival (PFS) versus bevacizumab and placebo in women with newly diagnosed, advanced ovarian cancer following prior treatment with platinum-based chemotherapy and bevacizumab (HR 0.59; 95% CI 0.49-0.72; P <.0001). The benefit with olaparib was seen across all patient subsets but was more pronounced in patients with BRCA1/2 mutations and homologous recombination deficiency.

Data from the phase III PRIMA study are of particular importance as niraparib (Zejula) is currently under priority review, says Mirza. In the trial, frontline maintenance therapy with niraparib improved median PFS versus placebo in patients with newly diagnosed, platinum-sensitive disease, irrespective of biomarker status.

Though, the median PFS benefit was more pronounced in patients with BRCA mutations (HR, 0.40; 95% CI, 0.27-0.62; P < 0.001) versus the overall population (HR, 0.62; 95% CI, 0.50-0.75; P <.001).

The decision of which drug to use has to be taken on an individualized basis, says Mirza.

Finally, data from the phase III VELIA trial demonstrated that the frontline combination of veliparib and chemotherapy followed by veliparib maintenance resulted in a PFS benefit versus placebo and chemotherapy in patients with high-grade serous ovarian cancer. Median PFS was 23.5 months compared with 17.3 months in the veliparib/chemotherapy and placebo/chemotherapy arms, respectively (HR, 0.68; 95% CI, 0.56-0.83; P <.001). Notably, frontline veliparib/chemotherapy plus placebo maintenance did not show an improvement in PFS versus chemotherapy/placebo plus placebo maintenance.

VELIA marks the first randomized trial exploring platinum-based chemotherapy plus a PARP inhibitor. The combination is thought to have a synergistic effect whereby chemotherapy damages circulating tumor DNA and PARP blocks cell repair, says Mirza.

Going forward, Mirza is hopeful that ongoing research will lead to treatments with fewer adverse events and longer remissions.