Clinical Trial Finds Oral Drug Keeps Cancer Treatment on Track for Patients Who Develop Persistently Low Platelet Counts

In a phase 2 trial of patients with gastrointestinal cancers, avatrombopag helped 70% of those receiving chemotherapy to stay on treatment schedule, compared with 17% receiving placebo.

In a phase 2 clinical trial, Mass General Brigham Cancer Institute researchers found that the oral drug avatrombopag was safe and effective in managing persistent chemotherapy-induced thrombocytopenia (CIT) in more than half of patients with gastrointestinal cancers, offering a potential new option for managing a common and challenging complication from cancer treatment. Their work is published in the Journal of Clinical Oncology.

CIT occurs when chemotherapy lowers platelet levels, reducing the blood cells that help control bleeding. For patients receiving chemotherapy, low platelet counts are common and frequently lead to treatment delays or dose reductions of chemotherapy. This compromises vital cancer care, potentially reducing the chance of cure or length of survival in these patients. However, there are currently no widely available approved therapies to address this complication.

“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 CIT, which has historically been a very challenging complication to manage.”

Researchers enrolled 47 adults with gastrointestinal cancers and persistent CIT from across four U.S. cancer centers, including Massachusetts General Hospital, and randomly assigned them to receive avatrombopag or a placebo. Participants ranged from 25 to 84 years old; 30% were women, 17% were non-White, and 11% were Hispanic or Latino. The study was stopped early after an independent monitoring board determined that the trial had met its prespecified stopping criteria for efficacy.

Investigators found that 70% of patients receiving avatrombopag achieved successful treatment of CIT, defined as platelet recovery and prevention of chemotherapy delays or dose reductions, compared with 17% of those receiving placebo. Platelet counts recovered in 83% of patients who received the drug, compared with 46% of those who did not. No serious adverse events were attributed to avatrombopag, and no patients required platelet transfusions.

The authors note that further research is needed to determine whether improving CIT management leads to improved long-term outcomes.

Authorship: In addition to Al-Samkari, Mass General Brigham authors include Elizabeth P. Walsh, Colin D. Weekes, Pamela G. Hodges, Shilton E. Dhaver, Nina Strojny, Carolyn Donovan and Christos Belibasakis. Additional authors include Joseph J. Shatzel, Sandhya R. Panch, Julia H. Keating, Adel Kardosh, Stacey A. Cohen, Jonathan J. Cohen and Gerald A. Soff.

Disclosures: Al-Samkari discloses a consulting or advisory role for Sobi. Al-Samkari and Soff receive research funding from Sobi. Sobi also supplied avatrombopag and matching placebo tablets for the study.

Additional disclosures can be found in the paper.

Funding: This study was supported by an investigator-initiated study grant from Sobi to Massachusetts General Hospital.

Paper cited: Al-Samkari, H et al. “Avatrombopag Versus Placebo for Persistent Chemotherapy-Induced Thrombocytopenia in GI Cancers: The Phase II ACT-GI Trial” Journal of Clinical Oncology DOI: 10.1200/JCO-26-00568