Avatrombopag (TPO-R agonist) sharply improves platelet recovery and “on-time” chemo delivery in persistent CIT (ACT‑GI)

ACT‑GI (NCT05772546) randomized patients with gastrointestinal malignancies and persistent chemotherapy‑induced thrombocytopenia (Plt <85×10^9/L on day 1 of a planned cycle) to avatrombopag 40mg PO daily vs placebo in a lead‑in (chemo held up to 2 weeks) then one on‑cycle full‑dose chemo cycle if Plt recovered to ≥100×10^9/L. At a prespecified interim analysis, the DSMB stopped enrollment for efficacy: 70% (16/23) on avatrombopag met the composite primary endpoint (Plt ≥100×10^9/L within lead‑in and maintained ≥100×10^9/L at cycle end) vs 17% (4/24) on placebo (p<0.001); end‑of‑cycle median platelets were 157 vs 72×10^9/L, and no patients required platelet transfusion. Safety showed more AEs/SAEs with avatrombopag (74%/13% vs 46%/0%), with no study‑drug–related SAEs and no discontinuations/deaths attributed to study drug; bleeding events occurred in 2 avatrombopag patients (including 1 intracranial hemorrhage). Versus current “SOC” for CIT—dose delays/reductions and transfusions mainly reserved for severe thrombocytopenia/bleeding risk (often prophylaxis around ~10×10^9/L in stable patients)—these data suggest a pharmacologic path to preserve dose intensity in a population where there is no FDA‑approved CIT therapy.