Abstract 740P
Background
We did a single-arm phase II trial, we aim to investigate the efficacy of combining VEGFR2 inhibitor Apatinib with Gemcitable-docetaxel (Gem-tax) chemotherapy for resectable pulmonary metastases (PMs) of osteosarcoma. The pathological study of the post-surgical specimens were further presented here.
Methods
Of the 43 pts enrolled in this study, 37 tumor samples after metastasectomy were available for further pathological study. We evaluated the tumor / stromal component of the metastatic osteosarcoma, as well as the major components of the immune microenvironment. We also included metastasectomy osteosarcoma samples following Apatinib-only (n=7) and Gem-tax-Only (n=7) from historical control as a pragmatic comparison.
Results
The post-metastasectomy specimens of osteosarcoma were composed of 4 major components measured by the percentage of area in the tumor bed, including immune cell (mean area 9.8%), bone matrix (42.3%), chondral matrix (2.2%) and tumor cell (45.7%). Within the tumor cell region, the mean percentage of necrotic region, hyalinization and viable cell region were 43%,18.6% and 38.4%. We found that tumor necrosis rate was significantly different between Pts who reached the endpoint (R) or did not reach the endpoint (NR) (p<0.05). Furthermore, we found that antiangiogenics+chemotherapy combination group demonstrated the lowest proportion of viable tumor cells (37.9%) than Apatinib-only (84.7%) or Gem-tax-Only (73.2%), as well as the lowest expression of CD31 than the other two groups, suggested a potential synergy in anti-angiogenesis and cytotoxic activity. Interestingly, Apatinib-only group demonstrated a significantly higher infiltration of CD8+, PDL-1+ and FoxP3 + cells and TILs than the Gem-Tax-only group, with the combination group in between. In contrast, VEGFR2 expression as well as various immune components did not predict R versus NR patients.
Conclusions
Our translational study provides further mechanistic insight into the use of antiangiogenics-chemotherapy combination therapy and raises new possibilities for improving the armamentarium toward metastatic osteosarcoma.
Clinical trial identification
NCT03742193.
Editorial acknowledgement
Legal entity responsible for the study
Shanghai Jiaotong University, Ruijin Hospital.
Funding
Chinese Anticancer Association (CACA).
Disclosure
All authors have declared no conflicts of interest.