In a phase II study (OLIE) reported in JAMA Oncology, Gaspar et al found that the addition of lenvatinib to ifosfamide/etoposide did not significantly improve progression-free survival in children or young adults with relapsed or refractory osteosarcoma.
Study Details
In the global open-label trial, 81 patients (aged 2–25 years) with high-grade osteosarcoma who had received one to two lines of prior systemic treatment were randomly assigned between March 2020 and November 2021 to receive lenvatinib at 14 mg/m2 once daily with up to five 21-day cycles of ifosfamide at 3,000 mg/m2 and etoposide at 100 mg/m2 on days 1 to 3 of each cycle (n = 40) vs ifosfamide/lenalidomide alone. Patients randomly assigned to ifosfamide/etoposide could cross over to receive lenvatinib upon disease progression. The primary endpoint was progression-free survival on independent imaging review, with a prespecified one-sided significance threshold of .025.
Key Findings
Median follow-up was 12.2 months (95% confidence interval [CI] = 9.5–14.1 months). Median progression-free survival was 6.5 months (95% CI = 5.7–8.2 months) in the lenvatinib group vs 5.5 months (95% CI = 2.9–6.5 months) in the control group (hazard ratio [HR] = 0.54, 95% CI = 0.27–1.08, one-sided P = .04). The rate at 4 months was 76.3% vs 66.0%.
A total of 14 patients in the control group (34.1%) crossed over to receive lenvatinib. Median overall survival was 11.9 months (95% CI = 10.1 months to not estimable) in the lenvatinib group vs 17.4 months (95% CI = 14.2 months to not estimable) in the control group (HR = 1.28, 95% CI = 0.60–2.70, one-sided nominal P = .75).
Among the 39 patients in each group in the safety population, grade ≥ 3 treatment-related adverse events occurred in 35 patients (89.7%) in the lenvatinib group vs 31 patients (79.5%) in the control group. Treatment-related serious adverse events occurred in 59.0% vs 30.8% of patients. Treatment-related pneumothorax occurred in 17.9% vs 0% of patients.
The investigators concluded: “Although [lenvatinib plus ifosfamide/etoposide] did not meet prespecified statistical significance for improved [progression-free survival] vs [ifosfamide/etoposide], this study demonstrates the importance of international collaboration and randomized clinical trials in patients with relapsed or refractory osteosarcoma and may inform future trial design.”
Nathalie Gaspar, MD, PhD, of the Department of Oncology for Child and Adolescent, Gustave Roussy Cancer Campus, Villejuif, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by Eisai Inc and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of all study authors, visit JAMANetwork.com.
