The PRIMA/ENGOT-OV26/GOG-3012 (PRIMA) double-blind, placebo-controlled, phase 3 trial illustrated that niraparib resulted in improvement in progression-free survival (PFS) in patients with newly diagnosed, advanced, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response to first-line platinum-based chemotherapy. This analysis of data from the PRIMA study aimed to determine the impact of age on the efficacy and safety of niraparib.
Patients were initially randomized (2:1) to receive a fixed starting dose of 300 mg niraparib or placebo once daily. However, this protocol was amended to allow for individualization of the starting dose. For patients with a body weight <77 kg or platelet count <150,000/μL, the starting dose of niraparib was 200 mg once daily. For all other patients, the starting dose of niraparib was 300 mg once daily. For an analysis of efficacy and safety of niraparib versus placebo in older patients, the 733 enrolled patients from the PRIMA study were divided by age-group: <65 years versus ≥65 years. The primary end point of the study was PFS.
Of the 444 patients aged <65 years, 297 received niraparib while 147 received placebo. Of the 289 patients aged ≥65 years, 190 received niraparib while 99 received placebo. Efficacy was comparable between both age-groups. In patients aged <65 years, PFS was 13.9 months and 8.2 months for those taking niraparib and placebo, respectively (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.47-0.81). For patients aged ≥65 years, PFS was 13.7 months and 8.1 months for those taking niraparib and placebo, respectively (HR, 0.53; 95% CI, 0.39-0.74). In addition, both age-groups experienced similar types and frequency of any-grade and grade ≥3 treatment-emergent adverse events (TEAEs). For those aged <65 years receiving niraparib, any-grade events were experienced by 63.6% for thrombocytopenia, 62.9% for anemia, 51.7% for leukopenia, and 17.0% for hypertension. For those aged ≥65 years receiving niraparib, any-grade events were experienced by 70.5% for thrombocytopenia, 66.3% for anemia, 46.8% for leukopenia, and 19.5% for hypertension. For patients aged <65 years receiving niraparib, TEAEs grade ≥3 were experienced by 34.4% for thrombocytopenia, 33.3% for anemia, 21.4% for leukopenia, and 4.8% for hypertension. For those aged ≥65 years receiving niraparib, TEAEs grade ≥3 were encountered in 45.8% for thrombocytopenia, 27.4% for anemia, 22.1% for leukopenia, and 8.4% for hypertension.
A difference in grade ≥3 thrombocytopenia events was illustrated when comparing patients treated with a fixed starting dose of niraparib versus those treated with an individualized starting dose. For patients aged <65 years, 42.8% receiving a fixed dose and 18.0% receiving an individualized dose experienced grade ≥3 thrombocytopenia events. For patients aged ≥65 years, the results were 57.0% versus 26.1% for fixed versus individualized dose, respectively. Patient-reported outcomes and quality of life were assessed by FOSI and EQ-5D-5L and were found to be similar in both age-groups.
The authors completed the same type of analyses showing similar results when using a patient group age division threshold of 75 years versus 65 years, and concluded that age did not affect the efficacy and safety profile of niraparib and did not impact quality of life associated with niraparib treatment. However, individualized starting doses do improve the rate of grade ≥3 thrombocytopenia events.
Abstract and Poster 819P. ESMO 2020. September 19-21, 2020. Efficacy and safety of niraparib in older patients (pts) with advanced ovarian cancer (OC): results from the PRIMA/ENGOT-OV26/GOG-3012 trial.