615P - Pulmonary resectable metastases of osteosarcoma with apatinib and chemotherapy (PROACH): An open-label, single-arm phase II clinical trial

Background

Vascular endothelial growth factor receptor (VEGFR) inhibitors have demonstrated promising activity for recurrent and unresectable osteosarcoma. However, the use of VEGFR inhibitor for pulmonary metastatic osteosarcoma to improve resectability and postoperative outcome remains unexplored.

Methods

We did a single-arm phase 2 trial investigating the efficacy of adding anti-angiogenics to chemo for resectable pulmonary metastases (PMs) of osteosarcoma. Pts received VEGFR inhibitor Apatinib plus gemcitabine-docetaxel for 3 cycles pre- and 4 cycles post-metastasectomy, followed by Apatinib monotherapy maintenance until disease progression or unacceptable toxicities. Our primary endpoint was 12-month progression-free rate (12m-PFR) with a historical control of <30%. The primary endpoint would be met if ≥17 out of 39 evaluable pts were considered non-progression, corresponding to a pre-specified 12m-PFR of 50%.

Results

We enrolled 43 pts from Mar 2019 to Nov 2022 in this study, with 23 (54%) having ≥4 PMs, 12 (28%) having ≥10 PMs, and 24 (56%) having bilateral PMs. Extra tiny PMs were commonly detected and resected during surgical exploration. 39/43 pts (91%) finished their surgical procedures as planned, while 1 pt encountered tumor progression before metastasectomy and 3 failed to undergo the 2nd-stage metastasectomy after the 1^st stage. Two pts were excluded from efficacy analysis due to major protocol violations. Of the remaining 41 pts, tumor volume reduction was seen in 30 (73.2%) pts before surgery, and 18 of the first 39 evaluable pts were progression-free at 12m (primary endpoint met). In the safety analysis (43 pts), ≥grade 3 toxicities were noticed in 29(67%) pts. One of the 15 deaths was due to post-operative complications and the remaining (14/15) due to tumor progression. The most common grade 3–4 toxicies were thrombocytopenia (26%), proteinuria (16%), anemia (14%), granulocytopenia(12%), pain(9.3%), pneumothorax(9.3%). Of note, only 2 ≥grade 3 postoperative wound problems following VEGFR inhibitor were observed.

Conclusions

Our study demonstrated a potential activity of combining Apatinib plus chemotherapy with metastasectomy for treating pulmonary metastatic osteosarcoma.

Clinical trial identification

NCT03742193.

Editorial acknowledgement

We are wholeheartedly gratefull to all participants and their parents in this study.

Legal entity responsible for the study

Ruijin Hospital, Shanghai Jiaotong University.

Funding

Shanghai Municipal Health Commission (grant No. 202140124) National Science Foundation of China (grant No. 82141116) Natural Science Foundation of Shanghai (grant No. 20ZR1434000).

Disclosure

All authors have declared no conflicts of interest.