A phase II, multicenter, placebo-controlled trial of apatinib in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after two previous treatment regimens.

Abstract

7548 Background: Apatinib is an oral, small molecular tyrosine-kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR). Phase II study has showed that apatinib significantly improved the outcome of patients with advanced or metastatic gastric cancer (Li J, et al. ASCO 2011). The primary object of this study is to determine whether apatinib can improve progression free survival (PFS) compared with placebo in patients with advanced non-squamous NSCLC who failed two lines of treatment. Methods: This study recruited histologically diagnosed advanced non-squamous NSCLC patients who failed more than two lines of treatment including EGFR TKIs. Other eligible criteria included ECOG ≤1, adequate organ function and no prior exposure to VEGFR-TKI. The patients were randomized to receive apatinib at a dose of 750 mg or placebo (at allocation ratio of 2:1) orally once daily until the disease progression or unacceptable toxicity. Results: 135 patients (90 in apatinib arm, 45 in placebo arm) were included at 20 centers in China until Aug 2011. Median PFS was 4.7 months for apatinib group versus 1.9 months for placebo group, hazard ratio (HR) was 0.278 (95% CI 0.170, 0.455) (p<0.0001). The response rate (RR) and disease control rate (DCR) were also significantly better in study arm (12.2% and 68.9%) than in placebo arm (0% and 24.4%)(P=0.0158 and P<0.0001). The most frequently observed AEs were hypertension, proteinuria, and hand-foot syndrome (HFS). These AEs were generally mild or moderate in severity and were manageable. Conclusions: This randomized phase II trial shows that apatinib has substantial clinical activity without significant additional toxicity in patients with advanced non-squamous and non-small cell lung cancer. Continued investigation of apatinib is warranted in future clinical studies.

Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer

“…Most AEs in phase IIb with apatinib dose of 500 mg/day were, however, mild to moderate (grades 1-2, see Table 2), with the safety profile of the lower dose of apatinib seen in our phase IIb cohort comparable, and likely lower, to those seen in other single-agent apatinib studies in patients with advanced cancer. 21,22 Thus, a starting dose of apatinib 500 mg rather than the originally reported 750 mg 22 may be warranted, either as a single agent in patients with heavily pretreated metastatic TNBC or in other phase III trials testing apatinib in earlier disease stages, with or without chemotherapy.…”

“…20 Two subsequent randomized phase II trials have found that when compared to placebo arms, the objective response rate (ORR), disease control rate (DCR), and PFS were significantly improved with apatinib monotherapy as second-or third-line treatment of metastatic gastric and lung cancers. 21,22 We report here results from NCT01176669, a prospective, open label, phase II multicenter trial coordinated by Fudan University Shanghai Cancer Center to evaluate the efficacy and safety of apatinib as a single agent in heavily pretreated patients with metastatic TNBC.…”

Apatinib monotherapy for advanced non‐small cell lung cancer after the failure of chemotherapy or other targeted therapy

“…Zhang et al conducted a phase II trial to determine whether apatinib could improve PFS compared to a placebo in patients with advanced non-squamous NSCLC who had failed two lines of therapy. 19 Ninety patients were randomized to apatinib 750 mg until disease progression or unacceptable toxicity. The trial showed that apatinib has a substantial clinical effect without severe additional AEs in patients with advanced NSCLC.…”

Successful treatment using apatinib with or without docetaxel in heavily pretreated advanced non-squamous non-small cell lung cancer: A case report and literature review

“…[12][13][14][15] A phase II, multicenter, placebo-controlled trial of apatinib showed a significant improvement in the median PFS, objective response rate and disease control rate compared to placebo in patients with advanced non-squamous NSCLC who failed two lines of treatment. 10 A phase III clinical trial is underway to validate these findings (NCT02332512). A recent study indicated that apatinib exerted its anti-tumor effect via the inhibition of migration and invasion by inhibiting the RET/Src signaling pathway in NSCLC.…”

“…9 Furthermore, a previous phase II trial has shown the survival benefit of apatinib monotherapy in advanced NSCLC. 10 However, few studies have reported the efficacy of apatinib combined with chemotherapy in advanced non-squamous NSCLC.…”