ARIEL3 is a randomized, double-blind, placebo-controlled, phase 3 study investigating the poly (ADP-ribose) polymerase (PARP) inhibitor rucaparib as maintenance therapy versus placebo in patients with recurrent ovarian cancer regardless of biomarker status. The patients were randomized 2:1 to receive rucaparib 600 mg twice daily (n = 372) or placebo (n = 189) until disease progression or treatment discontinuation due to toxicity or other reasons. Safety was monitored for all patients who received at least 1 dose of rucaparib.
The median duration of treatment was 8.3 months (range, 0-67 months) for patients taking rucaparib and 5.5 months (range, 0-68 months) for those taking placebo. In the rucaparib arm, 62.1% (372) of patients experienced at least 1 treatment-emergent adverse event (TEAE) of grade ≥3, while in the placebo arm, only 16.4% (31) of patients experienced a TEAE. Discontinuation due to TEAEs (separate from discontinuation due to disease progression) occurred in 17.2% of patients in the rucaparib study arm, and in 1.6% of patients in the placebo arm. The most commonly reported TEAE (any grade) was nausea, which occurred in 76.3% of patients receiving rucaparib treatment and 37.0% of patients receiving placebo. Median time to first onset of nausea was 5 days (95% confidence interval [CI], 4-6) in the rucaparib arm and 17 days (95% CI, 7-57) in the placebo arm. Nausea was mostly grade 1 and was more common at the beginning of rucaparib treatment, declining from 66.9% in month 1 to 22.2% in month 24.
Asthenia/fatigue occurred in 71.8% of patients receiving rucaparib and 45.0% of patients taking placebo. Median time to first onset of asthenia/fatigue was 15 days (95% CI, 15-20) for rucaparib and 30 days (95% CI, 16-37) for placebo. Dysgeusia occurred in 39.8% of patients on rucaparib and 6.9% of patients receiving placebo. Median time of onset was 10 days (95% CI, 6-15) with rucaparib and 11 days (95% CI, 3-29) with placebo. The incidence of anemia/decreased hemoglobin was 39.5% with rucaparib and 4.8% with placebo. Median time of onset was 67 days (95% CI, 57-85) with rucaparib and 54 days (95% CI, 15-140) with placebo. Constipation was experienced by 37.9% of patients taking rucaparib and 23.3% of patients taking placebo. Median time of onset was 40 days (95% CI, 29-55) with rucaparib and 46 days (95% CI, 23-81) with placebo. Vomiting was experienced by 37.4% of patients taking rucaparib and 15.3% of patients taking placebo. Median time of onset for patients experiencing vomiting was 24 days (95% CI, 15-39) for rucaparib patients and 84 days (95% CI, 36-129) for patients taking placebo.
For the majority of frequently reported TEAEs of any grade, the median time to onset was ≤45 days and the mean duration of the first event was generally <60 days, with some TEAEs having first-onset times >45 days (anemia/decreased hemoglobin, abdominal pain, neutropenia/decreased neutrophils) or durations of approximately 90 to 160 days (asthenia/fatigue, decreased appetite, dysgeusia).
Abstract and Poster 821P. ESMO 2020. September 19-21, 2020. Timing of adverse events during maintenance treatment with rucaparib for recurrent ovarian cancer in the phase III ARIEL3 study.