Patient-reported outcomes of tolerability with adavosertib indicated greater incidence of fatigue, diarrhea, mucositis, and difficulty swallowing in patients receiving adavosertib and gemcitabine; however, no significant differences were noted in the symptomatic adverse-event profile for gastrointestinal events and anxiety.
A randomized, double-blind, placebo-controlled phase 2 trial (NCT02151292) compared gemcitabine in combination with either the WEE1 inhibitor, adavosertib, or placebo in women with platinum-resistant epithelial ovarian cancer. Patient-reported outcomes of tolerability were reported at the 2021 American Society of Clinical Oncology Annual Meeting.
Eligible patients received either adavosertib or placebo (days 1-2, 8-9, and 15-16) with gemcitabine (days 1, 8, and 15) in a 28-day cycle. The objectives of the study were to characterize frequency, severity, and/or interference of symptomatic adverse events (AEs; scored 0-4; higher scores indicating worse AEs) in the first 3 months of therapy, as measured by 12-week area under the curve (AUC12w) over time, and incremental AUC12w for adjustment to baseline symptomatic AEs.
The study enrolled 51 patients; of the 47 evaluable patients, 28 patients received adavosertib/gemcitabine, and 19 patients received placebo/gemcitabine. The majority of the study population had an Eastern Cooperative Oncology Group performance status ≤1. Patients in the adavosertib/gemcitabine arm received a median of 5 treatment cycles, and those in the placebo/gemcitabine arm received a median of 2 treatment cycles. More than 90% of patients completed the survey.
Patients who received adavosertib/gemcitabine indicated higher any-grade severity and interference for several AEs; mean AUC12w was significantly higher for fatigue severity and interference, diarrhea frequency, mucositis, and difficulty swallowing severity. No significant between-arm differences were noted in abdominal pain, bloating, nausea, vomiting, or anxiety. The incremental AUC12w was significantly higher in the adavosertib/gemcitabine arm compared with the placebo/gemcitabine arm for difficulty swallowing severity, mucositis severity, and fatigue severity. Compared with placebo, a significantly greater number of 3/4 scores per survey time were observed at cycle 1, day 15 for fatigue severity in the adavosertib/gemcitabine group (55% vs 19%; P = .044).
Patients’ perception of adavosertib-emergent toxicity indicated a higher incidence of fatigue, diarrhea, mucositis, and difficulty swallowing in patients receiving adavosertib and gemcitabine. However, no significant differences were noted in the symptomatic AE profile for nausea, vomiting, abdominal pain, bloating, or anxiety.
Source: Madariaga A, Mitchell SA, Pittman T, et al. Patient self-reporting of tolerability using PRO-CTCAE: a randomized double-blind placebo-controlled phase II trial comparing gemcitabine in combination with adavosertib or placebo in women with platinum resistant epithelial ovarian cancer. J Clin Oncol. 2021;39(suppl_15). Abstract 5541.