Avatrombopag successfully managed persistent chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer, according to findings from the randomized phase II ACT-GI trial published in the Journal of Clinical Oncology.
“Chemotherapy remains a cornerstone of therapy for gastrointestinal cancers, so we want patients to be able to stay on their planned treatment,” said lead and corresponding author Hanny Al-Samkari, MD, a classical hematologist at the Mass General Brigham Cancer Institute, the Peggy S. Blitz Endowed Chair in Hematology/Oncology at Mass General Brigham, and an Associate Professor of Medicine at Harvard Medical School. “The findings from our trial may help improve care for patients who experience persistent [chemotherapy-induced thrombocytopenia], which has historically been a very challenging complication to manage.”
Background and Study Methods
Avatrombopag is a potent, second-generation oral thrombopoietin receptor agonist currently used to treat adults with chronic immune thrombocytopenia who have had an insufficient response to prior treatment. Data supporting the use of thrombopoietin receptor agonists to treat persistent chemotherapy-induced thrombocytopenia have been limited.
Investigators conducted a multicenter, randomized, double-blind, investigator-initiated U.S. trial of avatrombopag vs placebo in patients with gastrointestinal cancers who had persistent chemtherapy-inducted thromboctyopenia, defined as platelet levels ≤ 85 x 109/L on day 1 of a chemotherapy cycle despite adequate time to recover from the prior chemotherapy cycle. Patients were randomly assigned to the investigational or control arm in a 1:1 ratio.
The primary endpoint was the correction of chemotherapy-induced thrombocytopenia and prevention of recurrence.
Key Findings
As of the planned interim analysis, the trial had met prespecificed stopping criteria for efficacy, and the trial was closed to further enrollment.
Seventy percent of patients (95% confidence interval [CI] = 47%–87%) in the avatrombopag arm achieved successful correction of their chemotherapy-induced thrombocytopenia and prevention of recurrence vs 17% (95% CI = 5%–37%) in the placebo arm (Z = 3.67; P < .001).
The median platelet count at the end of the on-cycle treatment period was 157 x 109/L (interquartile range [IQR] = 136–202 x 109/L) with avatrombopag compared with 72 x 109/L (IQR = 68–134 x 109/L) with placebo.
Adverse events were observed in 78% of patients on the avatrombopag arm vs 46% in the placebo arm; serious adverse events were reported in 17% and 0% of patients, respectively. No serious events were considered related to the study drug, and no treatment-related adverse events led to death or treatment discontinuation of the study drug.
"These findings are promising for a common, challenging oncologic complication that prevents delivery of full-dose, on-time, cancer-directed therapy," the study authors concluded.
DISCLOSURES: This study was supported by an investigator-initiated study grant from Sobi to Massachusetts General Hospital. For full disclosures of the other study authors, visit ascopubs.org.
