A double-blind, randomized, placebo-controlled, phase 2 trial compared gemcitabine in combination with the WEE1 inhibitor adavosertib or placebo in patients with platinum-resistant or refractory high-grade serous ovarian cancer (HGSOC). The adavosertib/gemcitabine arm demonstrated superior progression-free and overall survival. The PRO-CTCAE assessment was included as an exploratory objective of the study to collect self-reported frequency, severity, and/or interference of symptomatic adverse events (syAEs).
In order to characterize syAEs during the initial 3 months of therapy, PRO-CTCAE items were completed at baseline, days 1 and 15 of each cycle, and off treatment in 2 locations. Each patient’s greatest post-baseline score proportion for each syAE was recorded. The 12-week area under the curve (AUC12w) as a measure of syAEs over time, and the incremental AUC12w (iAUC12w) for adjusting syAEs from baseline. About 61 patients were contacted for PRO-CTCAE questionnaires, of which 55 were evaluable. About 28 patients with HGSOC received gemcitabine/adavosertib (arm A) and 19 individuals received gemcitabine/placebo (arm B) (arm B). The survey response rate was high. The proportion of participants with positive (≥1) PRO-CTCAE scores for difficulty swallowing was significantly greater with gemcitabine/advosertib (35.7% versus 5.3%, P = 0.02).
With gemcitabine/adavosertib, the syAEs with a high score (≥3) occurred more frequently (arm A 25% versus arm B 0%, P = 0.03). The proportions of syAEs that worsen with time were higher in patients receiving gemcitabine/adavosertib for trouble swallowing (arm A 35.7% versus arm B 5.3%; P = 0.03) and fatigue severity (arm A 71.43% versus arm B 42.5%; P = 0.04). The longitudinal study of patient self-reported tolerability revealed that gemcitabine/advosertib patients had more trouble swallowing and weariness than gemcitabine/placebo patients. PRO-CTCAE provides an additional and objective assessment of drug tolerability from the perspective of the patient.