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

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.

Fig. 1

Trial profile. ^*Two patients were excluded because they had no post-baseline efficacy assessment

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

Kaplan–Meier estimates for progression-free survival (a) and overall survival (b) in patients with at least one post-baseline efficacy assessment (n = 38)