Apatinib for advanced sarcoma: results from multiple institutions’ off-label use in China

Abstract

BackgroundAnti-angiogenesis Tyrosine kinase inhibitors (TKIs) have been proved to show promising effects on prolonging progression-free survival (PFS) for advanced sarcoma after failure of standard multimodal Therapy. Methylsulfonic apatinib is one of those TKIs which specifically inhibits VEGFR-2. This paper summarizes the experience of three Peking University affiliated hospitals in off-label use of apatinib in the treatment of extensively pre-treated sarcoma.MethodsWe retrospectively analysed files of patients with advanced sarcoma not amenable to curative treatment, who were receiving an apatinib-containing regimen between June 1, 2015 and December 1, 2016. Fifty-six patients were included: 22 osteosarcoma, 10 Ewing’s sarcoma, 3 chondrosarcoma and 21 soft tissue sarcoma.ResultsWith median follow-up time of 6 months (range, 0.7–18.0 m), thirty-five (62.5%) patients had partial response, and disease was stable in 11 (19.6%). The 4-month and 6-month progression-free survival rates were 46.3 and 36.5%, respectively. The median duration of response was 3.8 months (95% CI 1.9–5.6 m), with much variability among disease subtypes. The median overall survival was 9.9 months (95% CI 7.6–12.2 m). Grade 3 and 4 toxicities were observed in 8 (14.3%) patients, the most common being hypertension, pneumothorax, wound-healing problems, anorexia, and rash or desquamation.ConclusionsApatinib might be effective, with a high objective response rate, in an off-label study of sarcoma patients with advanced, previously treated disease. The duration of response was consistent with reports in different subtypes of sarcomas. Prospective trials of apatinib in the treatment of selected subtypes of sarcomas are needed.Trial registrationRetrospectively registered in the Medical Ethics Committee of Peking University People’s Hospital, Peking University Shougang Hospital and Peking University International Hospital. The trial registration number is 2017PHB176–03 and the date of registration is January 20th 2017.

Management of recurrent or refractory Ewing sarcoma: A systematic review of phase�II clinical trials in the last 15�years

“…NCT02243605) in patients with EWS look promising, and an ORR of 28.1% in 32 patients was observed, as well as a high tumor burden reduction rate of 71% (38). For apatinib, which is also a strong aaTKI (39), an ORR of 70% (7/10) was observed in an off-label set of patients with EWS (33). Based on these data, it was concluded that aaTKIs require further investigation.…”

“…Only regorafenib, which has a stronger anti-angiogenesis effect, demonstrated promising clinical activity in patients with EWS. Further trials for other types of aaTKI, including pazopanib, cabozantinib and apatinib, which have shown some activity in other types of sarcoma (31)(32)(33), are ongoing and the results of which are anticipated. For patients who were refractory to first-line chemotherapy, pazopanib was reported to be effective in a set of case series (34-37).…”

Analysis of metabolome changes in the HepG2 cells of apatinib treatment by using the NMR‐based metabolomics

“…1,2 The apatinb was applied on prolonging progression-free survival of advanced sarcoma when the standard multimodal therapy was failure. 3 In previous research, the clinical presentation of apatinib in advanced non-small-cell lung cancer showed its effective and well tolerated in patients. 4 Most studies have shown that apatinib has encouraging efficacy and controllable side effects in the treatment of a variety of solid tumor.…”

“…Apatinib is the world's first small‐molecule‐drug of selective vascular endothelial growth factor receptor‐2 tyrosine kinase inhibitor (TKI) that is proven to be safe and effective in advanced or metastatic gastric cancer . The apatinb was applied on prolonging progression‐free survival of advanced sarcoma when the standard multimodal therapy was failure . In previous research, the clinical presentation of apatinib in advanced non‐small‐cell lung cancer showed its effective and well tolerated in patients .…”

<p>Anorexia, Hypertension, Pneumothorax, and Hypothyroidism: Potential Signs of Improved Clinical Outcome Following Apatinib in Advanced Osteosarcoma</p>

“…1 Anti-angiogenesis tyrosine kinase inhibitors (TKIs) are effective in prolonging progression-free survival (PFS) for advanced osteosarcoma that has progressed upon firstor second-line chemotherapy. 2,3 In a prospective study on apatinib for advanced osteosarcoma after the failure of traditional multimodal therapy (NCT02711007), apatinib reached 4-month PFS rate of 56.8% for advanced osteosarcoma [4][5][6][7] with a tolerable and manageable safety profile. 5,[8][9][10] The administration of apatinib induced tumor shrinkage and showed a high objective response (43.2%), but the toxic effects were severe with high rates of dose reduction (59.5%).…”