Avatrombopag Effectively Treats Persistent Chemotherapy-Induced Thrombocytopenia in GI Cancers (ACT-GI Trial): JCO | August 2026

Introduction:

Chemotherapy-induced thrombocytopenia (CIT) is a common dose-limiting toxicity in patients with gastrointestinal (GI) cancers, often leading to treatment delays, dose reductions, or premature discontinuation of chemotherapy. Persistent CIT has been particularly difficult to manage, with limited evidence supporting effective pharmacological therapies. The Phase II ACT-GI trial evaluated whether avatrombopag, an oral thrombopoietin receptor agonist, could safely restore platelet counts and allow patients to continue planned chemotherapy.

Why was this study needed?

Persistent chemotherapy-induced thrombocytopenia frequently interrupts optimal cancer treatment.

Chemotherapy delays and dose reductions may compromise treatment efficacy and survival.

Effective treatment options for persistent CIT are limited.

Avatrombopag has proven efficacy in immune thrombocytopenia, but robust evidence in chemotherapy-induced thrombocytopenia has been lacking.

A safe strategy to maintain planned chemotherapy schedules is an important unmet clinical need.

Results:

The randomized, double-blind Phase II ACT-GI trial compared avatrombopag with placebo in patients with GI cancers experiencing persistent chemotherapy-induced thrombocytopenia.

The trial was stopped early after meeting its predefined efficacy criteria at interim analysis.

Seventy percent of patients receiving avatrombopag achieved successful correction of thrombocytopenia and prevention of recurrent CIT compared with 17% receiving placebo.

Patients treated with avatrombopag achieved substantially higher platelet counts, enabling recovery to levels suitable for continued chemotherapy.

Although adverse events were more frequently reported with avatrombopag, no serious adverse events were attributed to the study drug, and there were no treatment-related deaths or treatment discontinuations.

Overall, avatrombopag demonstrated an acceptable safety profile while effectively maintaining platelet recovery.

Clinical Impact:

The ACT-GI trial provides the strongest randomized evidence to date supporting avatrombopag as an effective treatment for persistent chemotherapy-induced thrombocytopenia in patients with GI cancers. By restoring platelet counts and preventing recurrent thrombocytopenia, avatrombopag has the potential to reduce chemotherapy delays and dose reductions, allowing patients to remain on potentially curative or life-prolonging treatment schedules. If confirmed in larger studies, avatrombopag could become an important supportive care strategy in gastrointestinal oncology.

Bottom Line:

Avatrombopag significantly improved platelet recovery and prevented recurrent chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancers, enabling continuation of planned chemotherapy with an acceptable safety profile. The ACT-GI trial establishes avatrombopag as a promising new option for managing one of the most challenging complications of cancer treatment.