Niraparib (Zejula) monotherapy in patients with advanced ovarian cancer significantly improved progression-free survival (PFS) following response to first-line chemotherapy, according to a late-breaking data presentation at the ESMO Congress 2019.

Niraparib was the first oral poly ADP ribose polymerase (PARP) inhibitor approved as maintenance treatment for all patients with recurrent ovarian cancer. Consistent with previous trials, the updated data confirm niraparib as the first PARP inhibitor to demonstrate benefit in patients across biomarker subgroups with recurrent disease.

In ovarian cancer, disease recurrence occurs in up to 85% of cases after completion of standard first-line platinum-based chemotherapy, lead study author Antonio Gonzalez, MD, co-director, department of medical oncology at Clinica Universidad de Navarra, said in the presentation. For this reason, there is still a high unmet need for many patients, even with the currently available maintenance therapy options.

The PRIMA/ENGOT-OV26/GOG-3012 phase 3 study evaluated the efficacy and safety of niraparib therapy after response to platinum-based chemotherapy in patients with newly-diagnosed ovarian cancer, including those at high risk of relapse.

Overall, niraparib treatment resulted in a 38% reduction in the risk of disease progression or death in the overall population (PFS, HR 0.62; 95% CI, 0.50-0.75; p<0.001).

The data demonstrated a clinically meaningful reduction in risk of progression in women with:
  • BRCA mutation tumors (risk reduction of 60%, HR 0.40 (95% CI, 0.27-0.62) p<0.001).
  • Homologous recombination (HR)-deficient BRCA wild type tumors (risk reduction of 50%, HR 0.50 (95% CI, 0.30-0.83), p=0.006).
  • HR-proficient tumors (risk reduction of 32%, HR 0.68 (95% CI, 0.49-0.94), p=0.020).
A pre-planned interim analysis also pointed to an encouraging trend in improved OS, favoring niraparib over placebo. However, median OS was not yet reached.

The 24-month OS rate at this point showed:
  • Overall population: 84% versus 77% alive at 2 years.
  • HR-deficient: 91% versus 85% alive at 2 years.
  • HR-proficient: 81% versus 59% alive at 2 years.
Additionally, no new safety signals were identified for niraparib, with the most common treatment-emergent adverse event being reversible myelosuppression, according to the study.

Dr Gonzalez indicated that these data support niraparib monotherapy after first-line platinum-based chemotherapy as a new standard of care.

In an interview with Pharmacy Times® and Specialty Pharmacy Times®, Mansoor Raza Mirza, MD, chief oncologist at Copenhagen University Hospital, called the data on PARP inhibitors from several different studies being presented at the congress “unprecedented.”

“We have not seen such results in the last 30 years, so this is really changing the history,” he said.

Watch Dr Mirza’s commentary on the latest PARP inhibitor data in the video below.  



References
  1. Gonzalez-Martin A, B Pothuri, Vergote I, et al. Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study). Presented at: ESMO Congress 2019, Barcelona, Spain, September 27 to October 1, 2019.