1724MO - The final results of pulmonary resectable metastases of osteosarcoma with antiangiogenic and chemotherapy (PROACH): An open-label, single-arm phase II clinical trial

Background

Tyrosine-kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) have emerged as a major advance for recurrent and unresectable osteosarcoma. However, the use of VEGFR inhibitors for resectable metastatic osteosarcoma has reached limited success.Tyrosine-kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) have emerged as a major advance for recurrent and unresectable osteosarcoma. However, the use of VEGFR inhibitors for resectable metastatic osteosarcoma has reached limited success.

Methods

We present the final result of PROACH study, in which we aim to investigate the efficacy of combining VEGFR2 inhibitor Apatinib(Apa) with Gemcitable-docetaxel(Gem-tax) chemotherapy for resectable pulmonary metastases (PMs) of osteosarcoma (NCT03742193). Pts received Apa plus Gem-tax for 3 cycles pre- and 4 cycles post-metastasectomy, followed by Apa-monotherapy maintenance until PD or unacceptable toxicities. The primary endpoint would be met if ≥17 of 39 evaluable pts were considered non-progression at 12m(PFR of 50%), compared to the historical control of <30%.

Results

From Mar 2019 to Nov 2022, 43 pts with resectable PMs were enrolled in this study. At baseline, 12 (28%) having ≥10 PMs, and 24 (56%) having bilateral PMs. With neoadjuvant Apa-Gem-Tex therapy, 39/43 pts (91%) fulfilled the metastasectomy procedures and 4 failed to undergo the full metastasectomy procedure due to tumor progression. For the efficacy analysis, 18 of the 39 evaluable pts were progression-free at 12m, indicating the primary endpoint of this study was met. Furthermore, tumor volume reduction was seen in 30 of 41 pts (73.2%) at the time of the 1^st PM surgery. The median tumor necrosis rate of our cohort is 90% (min-max, 35%-100%), significantly higher than Gem-Tex monotherapy control from the same institution. In the safety analysis, ≥grade 3 toxicities were noticed in 29 (67.4%) pts. The most common grade 3–4 toxicies were thrombocytopenia (25.6%), proteinuria (16.3%), anemia (14.0%), etc.

Conclusions

Our study provides the first evidence of adding antiangiogenics to conventional chemotherapy for resectable metastatic osteosarcoma.

Clinical trial identification

NCT03742193.

Editorial acknowledgement

Legal entity responsible for the study

Ruijin Hospital, Shanghai Jiaotong University.

Funding

China Anti-cancer Association (CACA).

Disclosure

All authors have declared no conflicts of interest.