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

Abstract

Background: Anti-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.

Methods: We 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.

Results: With 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.

Conclusions: Apatinib 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 registration: Retrospectively 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.

Keywords: Apatinib; Chondrosarcoma; Ewing sarcoma; Osteosarcoma; Soft-tissue sarcoma; Tyrosine-kinase inhibitor.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the institutional review board, Peking University People’s Hospital, Peking University Shougang Hospital and Peking University International Hospital Ethics Committee for Clinical Investigation. All those patients had signed informed consent forms for data collection and use for research purpose, of which children patients’ informed forms had be signed by their legal parents. The ethical approval reference number was IRBK-2017-019-01.

Consent for publication

All those patients had signed informed consent forms for data collection and publication, of which children patients’ informed forms had been signed by their legal parents.

Competing interests

The authors declare that they have no competing interests in this article.

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Figures

Fig. 1

Waterfall plot of best change from baseline for 22 osteosarcoma patients. Patients’ clinical evaluations are indicated on the vertical graph as total volume increase or decrease. The numbers on the horizontal graph indicate the number of months of duration response. Strips with black frame indicate follow-up not yet at end point, and the patients’ status might continue unchanged for some while

Fig. 2

Waterfall plot of best change from baseline for 10 Ewing sarcoma patients

Fig. 3

Waterfall plot of best change from baseline for 21 soft tissue sarcoma patients