Multicenter phase 2 trial of avatrombopag versus placebo for persistent chemotherapy-induced thrombocytopenia in GI cancers
Chemotherapy-induced thrombocytopenia (CIT) is a challenging complication of cytotoxic chemotherapy in patients with GI cancers. Avatrombopag is a second-generation oral thrombopoietin receptor agonist. The multicenter randomized phase 2 ACT-GI trial in the United States evaluated avatrombopag versus placebo in GI cancer patients with persistent CIT (platelets ≤ 85 x 109/L on day 1 of a chemotherapy cycle despite adequate time to recover from the previous cycle). The primary endpoint was successful correction of CIT and prevention of recurrence, defined as recovery of platelets to ≥ 100 x 109/L without chemotherapy dose modification or delay. The trial was closed to enrollment by the data and safety monitoring board at a planned interim analysis after meeting prespecified stopping criteria for efficacy. Sixteen of 23 patients (70%; 95% CI 47-97) in the avatrombopag group achieved the primary endpoint, versus 4 of 24 patients (17%; 5-37) receiving placebo (p<0.001). The median platelet count at the end of the on-cycle treatment period was 157 (IQR 68-134) x 109/L with avatrombopag versus 72 (68-134) x 109/L with placebo. Adverse events (AEs) and serious AEs occurred in 78% and 17% of patients receiving avatrombopag and 46% and 0% of patients receiving placebo, respectively. No serious AEs were study drug-related. There were no treatment-related AEs leading to death or study drug discontinuation. The authors conclude that avatrombopag was efficacious in the management pf persistent CIT in patients with GI cancers.