Dr Livingston on the Addition of Hydroxychloroquine to Gemcitabine/Docetaxel in Osteosarcoma

“We felt that this combination was active based on the 4-month EFS rate of 44%. To put that in perspective, when we look at historic controls of phase 2 data in this population, particularly those benchmarks published by the Children’s Oncology Group, we typically would think of 12% as a standard benchmark [for EFS rate].”

John Andrew Livingston, MD, MS, clinician, researcher, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, discusses follow-up data from a phase 1/2 trial (NCT03598595) evaluating gemcitabine, docetaxel, and hydroxychloroquine in patients with advanced, metastatic osteosarcoma.

This study assessed the safety and best dose of hydroxychloroquine and how well it works in combination gemcitabine and docetaxel in the treatment of patients with osteosarcoma that has come back or does not respond to treatment. Updated results presented during the 2024 ESMO Congress showed that the combination was well tolerated, prolonged stable disease (SD), and generated pathologic complete responses (CRs) in patients with osteosarcoma, Livingston begins. 

Given the challenges in measuring treatment efficacy in osteosarcoma, event-free survival (EFS) or progression-free survival are considered more relevant benchmarks as opposed to traditional tumor shrinkage metrics, Livingston explains. The study reported a 4-month EFS rate of 44% among all treated patients, which represents a substantial improvement in EFS compared with historical phase 2 data, he says. Notably, prior benchmarks published by the Children’s Oncology Group indicate that a 4-month EFS rate of approximately 12% is typical in this setting, Livingston adds. The combination also produced 1 CR, 13 instances of SD, and 11 instances of progressive disease per RECIST 1.1 criteria.

These results indicate that hydroxychloroquine, when combined with gemcitabine and docetaxel, demonstrates meaningful clinical activity in this population, Livingston states. In light of the limited treatment options for patients with relapsed or refractory osteosarcoma, these findings warrant further investigation in larger clinical trials, he concludes.