Ovarian cancer patients who receive Zejula (niraparib) after responding to platinum-based chemotherapy experience fewer adverse effects in a real-world setting than was reported in a Phase 3 clinical trial, a study found.

However, the lower rate of side effects “may be due to the higher dosing in the trial study,” researchers wrote.

The study, “Real world occurrence of top three clinical-trial reported adverse events of PARP inhibitor niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer, a national retrospective observational study of a 200 mg/day starting-dose cohort,” was presented last month at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany.

Zejula, developed by Tesaro, is a PARP inhibitor indicated for the maintenance of ovarian cancer patients who are in a complete or partial response to platinum-based chemotherapy.

The treatment was approved after positive data from the ENGOT-OV16/NOVA Phase 3 trial (NCT01847274), which compared Zejula (300 mg once daily) to a placebo as a maintenance treatment for ovarian cancer patients who had received at least two platinum-based chemotherapy regimens, and had achieved a partial or complete response to the most recent one.

In the trial, patients had started Zejula at a 300 mg daily dose, but most patients required a dose reduction due to treatment toxicity. After dose adjustments, the 200 mg dose was the most commonly prescribed.

Zejula significantly delayed disease worsening or death from 5.5 months to 21 months, reducing the risk of disease progression or death by 74% regardless of BRCA mutations — usually predictive of a response to PARP inhibitors.

Later quality-of-life assessments also demonstrated similar scores for patients receiving Zejula and placebo, suggesting the treatment delayed disease progression without taking a toll on quality of life.

However, researchers reported that nearly 60% of patients experienced nausea, fatigue, or thrombocytopenia (low platelet levels).

Now, researchers retrospectively examined safety data from 153 patients receiving Zejula in a real-world setting. Participants had either epithelial ovarian, fallopian tube, or primary peritoneal cancer, had responded to their last platinum-based chemotherapy, and received a starting dose of 200 mg per day of Zejula.

Within the first three months of treatment, 37% of patients experienced one of the three adverse side effects — nausea, fatigue, or thrombocytopenia — and 32% experienced only mild or moderate side effects.

Overall, 24% of patients reported fatigue, 16% said they had experienced nausea, and 14% had had low platelet levels — including 2% that were severe or life-threatening.

Overall, adverse side effects led to a dose interruption in 4% of patients, dose reduction in 11%, and treatment withdrawal in 2%.

“While over 60% of patients in the phase 3 clinical trial reported experiencing the three AEs [adverse events] observed in the study, only 37% reported such in real-world usage,” researchers wrote.

The findings suggest that patients in a real-world setting experience fewer adverse side effects than what had been reported in the ENGOT-OV16/NOVA Phase 3 trial, and Zejula may be even safer than previously thought.

Nonetheless, researchers point to the use of lower starting doses in their study as a possible explanation for the fewer side effects, and add that “additional real-world research is needed to understand the effects of niraparib dosing on [adverse events].”