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

Lu Xie, Jie Xu, Xin Sun, Xiaodong Tang, Taiqiang Yan, Rongli Yang, Wei Guo, Lu Xie, Jie Xu, Xin Sun, Xiaodong Tang, Taiqiang Yan, Rongli Yang, Wei Guo

Abstract

Aim: Apatinib, a specific tyrosine kinase inhibitor (TKI) that targets mainly vascular endothelial growth factor receptor-2 (VEGFR-2) as well as Ret, c-Kit and c-Src, has been assessed in patients with advanced osteosarcoma (phase II), the primary report of which has been published in PMID 30559126. This sub-study explored the potential signs of Adverse Events (AEs) for apatinib-treated osteosarcoma.

Methods: Participants with advanced osteosarcoma progressing upon chemotherapy received apatinib until disease progression or unacceptable toxicity. Toxicities, progression-free survival (PFS), and clinical benefit rate (CBR) following treatment were evaluated.

Results: Of the 41 patients recruited to the study, 37 received treatment and constituted the safety population. At data cut-off (December 30, 2017), median follow-up for safety was 7.37 (IQR, 6.33-11.07) months. The most common grade 3-4 AEs were pneumothorax (16.22%), wound dehiscence (10.81%), proteinuria (8.11%), diarrhea (8.11%), and skin reaction (8.11%). Only hypertension was an independent predictive factor for both PFS (hazard ratio [HR], 0.44; P = 0.07) and CBR (P = 0.07). Anorexia was also significantly related to a longer PFS in a Cox regression model (HR, 0.35; P =0.01). For CBR, pneumothorax and hypothyroidism showed more clinical benefit (P = 0.07 and 0.00, respectively).

Conclusion: The results of this study suggest that anorexia, hypertension, pneumothorax, and hypothyroidism might be markers for a favorable clinical outcome following apatinib-treated refractory osteosarcoma.

Keywords: apatinib; osteosarcoma; prognosis.

Conflict of interest statement

The authors declare that they have no conflicts of interest.

© 2020 Xie et al.

Figures

Figure 1
Figure 1
The percentage of participants who had AEs of interest and the median (95% CI) for the onset of first incidence of AEs of interest (any grade) in days.
Figure 2
Figure 2
Forest plots of HRs for disease progression in different AE subgroups.
Figure 3
Figure 3
Kaplan–Meier curves for PFS from patients who did or did not have anorexia.
Figure 4
Figure 4
Kaplan–Meier curves for PFS from patients who did or did not have hypertension.

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