Clinical Study

Apatinib in patients with extensive-stage small-cell lung cancer after second-line or third-line chemotherapy: a phase II, single-arm, multicentre, prospective study

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Abstract

Background

Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies.

Methods

Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate.

Results

Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand–foot syndrome, increased L-gamma-glutamyltransferase.

Conclusions

Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted.

Trial registration

NCT02945852.

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Acknowledgements

We thank the patients and their families who participated in this study, and we also thank Jiangsu Hengrui Pharmaceuticals Co. for providing apatinib.

Author contributions

Y.F., Y.-J.X., Z.-Y.H., H.-Y.L., X.-M.Y., L.G., K.-Y.C., J.Q., X.-L.X., J.Z., X.S., Y.J., N.H., F.-J.X., Y.-P.L., J.C. and W.-F.L. recruited patients for the study, collected, analysed and interpreted the data. Y.F., Y.-J.X. and Z.-Y.H. designed the study, tables and figures. P.Z. analysed and interpreted the data and designed the figures and tables. M.C. designed the study. W.-Z.X. analysed and interpreted the data. Development of the first draft was performed by Y.F. and Y.-J.X. All authors provided final approval to submit for publication.

Author information

Correspondence to Yun Fan.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was approved by Medical Ethics Committee of Zhejiang Cancer Hospital with the committee’s reference number: IRB-2016-124. The study was performed in accordance with the Declaration of Helsinki. All enrolled patients provided written informed consent before any study-specific procedures were performed.

Funding

This is investigator initiated trial and Jiangsu Hengrui Pharmaceuticals Company provided apatinib for this study, but was not involved in the study design, data collection, analysis and interpretation, article writing, or the decision to submit for publication. All authors had full access to raw data, and the corresponding author has final responsibility for the publication submission.

Data availability

All data included in this study are available upon request by contact with the corresponding author.

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