Efficacy and safety analysis of anlotinib combined with etoposide plus ifosfamide in the treatment of children and adolescents with pulmonary metastatic osteosarcoma.

Abstract

11525 Background: Osteosarcoma is a highly malignant and aggressive tumor, predominantly occurring in children and adolescents under 20 years of age. It exhibits early metastatic potential, with 15%–20% of patients presenting with distant metastasis at diagnosis. Among these, pulmonary metastases account for 85% of cases. The 5-year survival rate after pulmonary metastasis is <20%. This study retrospectively analyzes the efficacy and safety of anlotinib combined with etoposide and ifosfamide in treating pediatric and adolescent patients with pulmonary metastatic osteosarcoma. Methods: This study retrospectively screened children and adolescent patients with pulmonary metastatic osteosarcoma who received etoposide + ifosfamide ± anlotinib at Northwest Women's and Children's Hospital from May 2018 to December 2024. The study was divided into a combination group (anlotinib + etoposide + ifosfamide) and a control group (etoposide + ifosfamide). The dosage of anlotinib: 8 mg for patients < 12 years old, qd, d1-d14, q3w, 12mg for patients ≥12 years old, qd, d1-d14, q3w. Treatment continued until disease progression or intolerable toxicity, with a maximum of 4 chemotherapy cycles. The primary endpoint of the study was objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival rate (PFSR), and safety. Results: The data cut-off date was December 2024, The study enrolled 38 patients (combination group: n=18, control group: n=20). Efficacy analysis showed the combination group achieved higher ORR (22.2% vs 15%, p =0.057) and significantly better DCR (66.7% vs 45%, p =0.015), and 3-month progression-free survival rates (PFSR) of 44.0% versus 30%. Subgroup analysis indicated superior outcomes with 12 mg versus 8mg anlotinib ( p <0.05). Biomarker evaluation revealed patients with high BRCA1/VEGFR2 expression had lower 3-year survival than those with intermediate/low expression, while low PDGFR expression was associated with poorer survival compared to intermediate/high levels. The combination group exhibited higher incidence rates of treatment-related adverse events (TRAEs) compared to the control group, including epistaxis (44.4%), hand-foot syndrome (27.8%), abnormal thyroid function (22.2%), and proteinuria (16.7%). All reported adverse events were grade 1-2 in severity, with no grade 3-4 severe adverse reactions observed. Conclusions: The combination therapy of anlotinib with ifosfamide and etoposide demonstrated superior efficacy compared to chemotherapy alone in pediatric patients with pulmonary metastatic osteosarcoma, showing higher ORR, DCR, and 3-month PFSR. These results indicate that anlotinib combined with neoadjuvant chemotherapy can more effectively delay tumor progression and prolong progression-free survival in these patients.