Rates of Niraparib-Related AEs Markedly Lower in Real World Compared With Clinical Trial

November 7, 2018
Wayne Kuznar

The rate of the 3 most common adverse events reported by US patients on niraparib who were started on 200 mg/day in real-world clinical practice is markedly less than the rate of AEs experienced by those enrolled in the pivotal phase III ENGOT-OV6/NOVA trial, in which patients were started at a 300-mg daily dose of niraparib, according to data presented at the 2018 ESMO Congress.


Using information from medical charts from the practices of randomly selected US physicians, a study led by Jack R. Gallagher found that the real-world incidences of nausea, thrombocytopenia, and fatigue were 2.5 to 4.5 times lower than that reported in NOVA trial.

More than 60% of patients in the NOVA trial reported experiencing the 3 AEs observed in the study, but only 37% reported such in real-world usage.

“The 300-mg dose is approved as the starting dose, so one of the questions we had was with a nationally representative study of patients: what would the AE rate be if the starting dose was 200 mg?” said Gallagher, MSc, chief scientist, Clarity Pharma Research, LLC. “We had a nationally representative study of hematologists and oncologists; of the 87 screened specialists, 61% participated, so the nonresponse bias wasn’t very high. The frequency of the top 3 AEs, including thrombocytopenia, the most serious one, was significantly lower than in the trials. We provide some evidence that it’s worth exploring a 200-mg starting dose and perhaps titrate up if you have to. It would probably be safer to do that.”

Niraparib has demonstrated efficacy in patients with platinum-sensitive, recurrent ovarian cancer. Nausea, thrombocytopenia, and fatigue were commonly occurring AEs in NOVA. Patients in the study were started at 300 mg/day of niraparib but after dose adjustments, a 200-mg daily dose was the most commonly administered dose.

A retrospective analysis of NOVA had suggested that the dose of niraparib could be adjusted due to AEs without having an impact on efficacy. In that analysis, patients with a baseline body weight&thinsp;<77&thinsp;kg or a baseline platelet count&thinsp;<150&thinsp;000/µl received an average daily dose of approximately 200&thinsp;mg due to dose interruption and reduction.2Progression-free survival in patients whose dose was reduced to either 200 or 100&thinsp;mg was consistent with that of patients who remained at the 300-mg starting dose.

In the study, 53 physicians were randomly selected from a national database (61% of qualified physicians screened). They extracted requested anonymous information from the electronic medical records of 153 qualified patients, defined as those who received a starting dose of 200&thinsp;mg/day of niraparib for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer and were in complete or partial response to platinum-based chemotherapy.

Sixty percent of patients had recurrent epithelial ovarian cancer, 24% had recurrent fallopian cancer, and 16% had primary peritoneal cancer. Two-thirds (67%) were 50 to 69 years old and 77% had an ECOG performance status of 0 or 1. The stage of cancer at original diagnosis was I in 13%, II in 19%, III in 48%, and IV in 20%. One-third (33%) received 1 line of chemotherapy prior to niraparib, 50% received 2 lines, 11% received 3 lines, and 6% received 4 or more lines.

Prior to starting niraparib, 58% of patients were in complete response to platinum-based chemotherapy and 42% had a partial response. Of the 65% who were tested for germlineBRCAmutation, 35% were known to have a germlineBRCA1mutation and 17% had a known germlineBRCA2mutation.

Thirty-seven percent of patients experienced a top 3 AE (all grades) within the first 3 months, 89% of which were not worse than grade 2 (10% were grade 3 and 2% were grade 4).

The rates of nausea of all grades were 73.6% in NOVA and 16.3% in clinical practice; the grade 3/4 rates of nausea were 3.0% and 1.3%, respectively.

The rates of all-grade thrombocytopenia were 61.3% in NOVA and 13.7% in the real-world setting; the rate of grade 3/4 thrombocytopenia was 16 times less in the real world at 2.0%, compared with 33.8% in NOVA.

The rates of fatigue (all grades) were 59.4% in NOVA and 23.5% in the real world; the rates of grade 3/4 fatigue were 8.2% and 5.2%, respectively.

Of the 153 patients, 6 (4%) had a dose interruption, 17 (11%) required dose reductions, and 3 (2%) discontinued niraparib altogether due to AEs.

The authors concluded that additional research is needed to further evaluate the effect of lower doses of niraparib than occurred in NOVA on frequency and severity of AE occurrence in real-world practice.


  1. Gallagher JR, Heap KJ, Carroll S. 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. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract 986P.
  2. Berek JS, Matulonis UA, Peen U, et al. Safety and dose modification for patients receiving niraparib.Ann Oncol.2018;29:1784-92. doi: 10.1093/annonc/mdy181.