The prognosis of metastatic bone and soft-tissue sarcoma remain distal. VEGFR2 inhibitor (VEGFR2i) has been recently found promising but is limited due to the heterogeneous durability of response.
From Jan 2016 to Jun 2018, 44 patients with lung metastatic sarcoma, including 32 osteosarcoma, 4 Ewing sarcoma, 3 leiomyosarcoma, 2 chondrosarcoma and 3 other sarcoma, given apatinib treatment were reviewed. Of these patients, extra-pulmonary lesions were noticed in 14 cases including local recurrence (9), bone (3), lymph node (2) and brain (1). A starting 250∼500 mg per day was chosen, with dose adjustment according to the individual tolerability. Progression-free survival (PFS) was accessed by RECIST 1.1 criteria and used to discover the potential predictor of durability of response.
The mean 6 month PFS was 58.9 +/- 8.4%, with the duration of response varying from 1 months to no less than 17 months. 12 of the 44 (27.3%) patients required a long-term dose lowering while the remaining well tolerated or has a dose transient lowering less than 7 days. Adverse effects (AEs) greater than degree 2 was seen in 50.0%, including pneumothorax in 11 cases (25.0%). In 9 of 11 cases with pneumothorax, no or minimal drug discontinuance was conducted, with 5 spontaneous recoveries, 3 recoveries with tube drainage, and 1 thoracic empyema with video-assisted thoracoscopic debridement. Multivariate analysis showed that AEs (HR = 0.29 p = 0.008) and sarcoma type (osteosarcoma vs other, HR = 0.17, p = 0.001) were the independent predictors for PFS with VEGFR2i therapy. Surprisingly, pneumothorax was found to be the strongest predictor among all AEs based on the effect size (HR = 0.29, p = 0.036), indicating that the susceptibility of pneumothorax to VEGFR2i might be a new mechanism-based toxicity biomarker for lung metastatic osteosarcoma.
Our result suggested that pneumothorax is a favorable biomarker for targeting VEGFR2 in lung metastatic sarcoma and we encourage no or minimal drug discontinuation in this circumstance.
Clinical trial identification
Legal entity responsible for the study
Ruijin Hospital, Oncological Orthopaedic Department.
Has not received any funding.
All authors have declared no conflicts of interest.