Apatinib is a VEGFR2 inhibitor that has shown promising anti-angiogenic and anti-tumor activity in preclinical and clinical studies. The potential of apatinib in reversing multidrug resistance, modulating the tumor microenvironment, and inhibiting tumor cell growth, proliferation, invasion, migration, metastasis, protective autophagy, and apoptosis. Apatinib is the star drug in advanced bone and soft tissue sarcoma.
The 2018 publication "Apatinib Advanced Sarcoma: Results of Off-Label Use by Multiple Institutions in China" discusses the off-label use of apatinib in patients with extensively experienced sarcomaDisplay62.Partial remission occurred in 5% of patients,19Six percent of patients had a stable high objective response rate。The 4- and 6-month progression-free survival rates were 46., respectively3% and 365%, with an overall median survival of 99 months. In terms of toxicity and safety, 14Grade 3 and 4 toxicity occurs in 3% of patients, including hypertension, pneumothorax, wound healing problems, loss of appetite, and rash or scaling.
The "Clinical Study of Stage IV Osteogenesarcoma After Chemotherapy Failure of Apatinib**" published in 2020 found that apatinib had good efficacy and tolerability, and the short-term efficacy showed an objective response rate of 6 at 12 weeks06%, and the disease control rate was 7879%。Median progression-free survival was 7At 89 months, the median overall survival was 1761 months.
On the issue of complications, the 2020 publication "Anorexia, hypertension, pneumothorax, and hypothyroidism: potential signs of improved clinical outcomes after apatinib in advanced osteosarcoma" evaluated adverse events (AES) in patients with advanced osteosarcoma receiving apatinib**. The most common grade 3-4 AEs observed in studies include pneumothorax, wound dehiscence, proteinuria, diarrhea, and ** reactions, at the same timeHypertension, anorexia, pneumothorax, and hypothyroidism were identified as predicting a better prognosis.
In order to achieve better results, there are studies to exploreApatinib in combination with PD-1 inhibitor** osteosarcomaeffect. Results from the 2020 publication "Advanced Osteosarcoma After Chemotherapy Progression with Apatinib in Combination With Camrelizumab (Anti-PD1 **SHR-1210)**: A Single-arm, Open-Label, Phase 2 Trial" showed a median PFS of 6At 2 months, the clinical benefit rate was 302%。Overexpression of PD-L1 and the presence of lung metastases are associated with longer PFS. However, the combination** did not meet the 6-month PFS target of 60% or higher. Adverse effects result in the need for dose reduction or discontinuation in many patients**.
For middle-aged and elderly patients with osteosarcoma who are intolerant to chemotherapy, the effect of apatinib alone is poor, and concomitant chemotherapy is still required. The "Activity and Safety of Apatinib Monotherapy** or Apatinib Plus Chemotherapy** in Patients Over 40 Years of Age: A Retrospective Analysis" published in 2022 concluded that median PFS and median OS were longer in the apatinib plus chemotherapy arm than in the apatinib monotherapy ** arm (56 months vs. 2.6 months;15.1 month vs. 9.7 months). In addition, the median DOR was significantly longer in the apatinib plus chemotherapy group compared to the single-agent** group.
Control of apatinib***In 2021, the "Management of Apatinib-related Adverse Events in Patients with Advanced Osteosarcoma in Four Prospective Trials: The Experience of the Chinese Sarcoma Research Group" published in 2021 ** describes the relevant management methods.
Summary: Apatinib has a good effect after the advanced stage and multi-line failure, so it has attracted the attention of many studies. However, such as hand and foot rash, high blood pressure, proteinuria, etc., cannot be ignored. Multiple regimens, such as combination chemotherapy**, may improve efficacy, and their optimization requires further investigation.
References: xie, l, guo, w., wang, y. et al. apatinib for advanced sarcoma: results from multiple institutions’ off-label use in china. bmc cancer 18, 396 (2018).
liao z, li t, zhang c, et al. clinical study of apatinib in the treatment of stage iv osteogenic sarcoma after failure of chemotherapy. cancer biol med. 2020;17(2):501-512.
lu xie, jie xu, xin sun, xiaodong tang, taiqiang yan, rongli yang & wei guo (2020) anorexia, hypertension, pneumothorax, and hypothyroidism: potential signs of improved clinical outcome following apatinib in advanced osteosarcoma, cancer management and research, 12:, 91-102.
xie l, xu j, sun x, et al. apatinib plus camrelizumab (anti-pd1 therapy, shr-1210) for advanced osteosarcoma (apfao) progressing after chemotherapy: a single-arm, open-label, phase 2 trial [published correction appears in j immunother cancer. 2020 jun;8(1):]j immunother cancer. 2020;8(1):e000798.
gong t, huang q, tang f, et al. activity and safety of apatinib monotherapy or apatinib combined with chemotherapy for patients with metastatic or unresectable osteosarcoma over the age of 40 years: a retrospective analysis. front oncol. 2022;12:1031787.
xie l, xu j, guo w, et al. management of apatinib-related adverse events in patients with advanced osteosarcoma from four prospective trials: chinese sarcoma study group experience. front oncol. 2021;11:696865.
liao z, li t, zhang c, et al. clinical study of apatinib in the treatment of stage iv osteogenic sarcoma after failure of chemotherapy. cancer biol med. 2020;17(2):501-512.