Apatinib for Treatment of Inoperable Metastatic or Locally Advanced Chondrosarcoma: What We Can Learn About the Biological Behavior of Chondrosarcoma from a Two-Center Study

PURPOSE: For patients who have chondrosarcoma in the unresectable setting, antiangiogenic agents are reportedly effective. This multicenter, retrospective study investigated the antitumor activity of apatinib in patients with unresectable chondrosarcoma to gain insight into the biological behavior of this disease. METHODS: All of the patients with unresectable chondrosarcoma who were diagnosed between October 1, 2009, and November 1, 2019, in two sarcoma centers affiliated with Peking University were evaluated. Relevant information was collected from the medical records at both centers, from which patients receiving apatinib for systemic therapy were selected for analysis. RESULTS: In total, efficacy analysis was conducted in 33 patients with a median follow-up time of 22.1 (Q1, Q3, 14.6, 23.0) months. There were 20/33 (60.0%) conventional chondrosarcomas (grades 2–3), 5/33 (15.2%) dedifferentiated chondrosarcomas, 4/33 (12.1%) mesenchymal chondrosarcomas, 3/33 (9.1%) extraskeletal myxoid chondrosarcoma, and 1/33 (3.1%) clear-cell chondrosarcomas with 87.9% in metastatic and 12.1% in locally advanced states. The objective response rate was 6/33 (18.2%). The median progression-free survival (PFS) was 12.4 months (Q1, Q3, 7.0, 21.2), while the median overall survival has not yet been reached. Rare variants of chondrosarcoma tended to have a longer PFS than conventional chondrosarcoma (P=0.06). Based on clinicopathological factors Cox and univariate analysis, only extraskeletal myxoid chondrosarcoma and baseline target lesions <60 mm benefited from the drug apatinib (P=0.14 and P=0.00), respectively. Grade 3 or higher adverse events were frequent in 11/33 (39.3%) of patients who discontinued apatinib due to deterioration of their general condition. CONCLUSION: Apatinib had clinically meaningful activity in patients with inoperable high-grade chondrosarcoma. However, special caution should be made in managing toxicity due to the indolent behavior and slow growth pattern after using this drug. Patients with a smaller tumor size and extraskeletal myxoid chondrosarcoma subtype might benefit from this therapy more. CLINICAL TRIAL REGISTRATION: Registered February 7, 2020, with clinicaltrials.gov: NCT04260113.