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

Yanjun Xu, Zhiyu Huang, Hongyang Lu, Xinming Yu, Yuping Li, Wenfeng Li, Jun Chen, Ming Chen, Lei Gong, Kaiyan Chen, Jin Qin, Xiaoling Xu, Ying Jin, Jun Zhao, Xun Shi, Na Han, Fajun Xie, Peng Zhang, Weizhen Xu, Yun Fan, Yanjun Xu, Zhiyu Huang, Hongyang Lu, Xinming Yu, Yuping Li, Wenfeng Li, Jun Chen, Ming Chen, Lei Gong, Kaiyan Chen, Jin Qin, Xiaoling Xu, Ying Jin, Jun Zhao, Xun Shi, Na Han, Fajun Xie, Peng Zhang, Weizhen Xu, Yun Fan

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Trial profile. *Two patients were excluded because they had no post-baseline efficacy assessment
Fig. 2
Fig. 2
Waterfall plot for the best percentage change in target lesion size (n = 38). Waterfall plot for the best percentage change in target lesion size is shown for 38 patients who had at least one post-baseline efficacy assessment. The colours indicate type of responses. The dashed line at 20% represents the boundary for determination of progressive disease, and the dashed line at –30% represents the boundary for determination of partial response. *Tumour shrinkage over 30% was observed in this patient, but there were new lesions, so it was judged to be disease progression
Fig. 3
Fig. 3
Kaplan–Meier estimates for progression-free survival (a) and overall survival (b) in patients with at least one post-baseline efficacy assessment (n = 38)

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