China National Medical Products Administration approval summary: anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy

Abstract

Background: On May 8, 2018, the China National Medical Products Administration (NMPA) approved anlotinib, an orally administered anti-angiogenesis inhibitor, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have progressed after treatment with two or more lines of prior systemic chemotherapy. China NMPA reviewed and inspected a regional double-blinded, placebo-controlled, Phase III trial comparing the overall survival (OS) of NSCLC patients between the anlotinib and placebo arms. A total of 437 patients were randomized (2:1) to receive either anlotinib (n = 294) or placebo (n = 143) once daily on a 2-week on and 1-week off schedule. Patients with epidermal growth factor receptor (EGFR) or activating anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on NMPA-approved therapy. Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China. The approval was based on a statistically and clinically significant improvement in median OS with anlotinib (9.46 months) compared with placebo [6.37 months; hazard ratio (HR]) = 0.70, 95% confidence interval (CI) = 0.55-0.89; two-sided log-rank P = 0.002]. The confirmed objective response rate (ORR) was 9.2% in the anlotinib arm and 0.7% in the placebo arm. The median duration of response (DoR) was 4.83 months, with a 95% CI of 3.31-6.97 months. The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors. Common adverse drug reactions (ADRs) in anlotinib-treated patients included hypertension (67.4%), hand-foot syndrome (43.9%), hemoptysis (14.0%), thyroid stimulating hormone (TSH) elevation (46.6%), and corrected QT interval (QTc) prolongation (26.2%).

Short conclusion: Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.

Keywords: Activating anaplastic lymphoma kinase; Advanced non-small cell lung cancer; Adverse drug reaction; Anlotinib; Anti-angiogenesis; Epidermal growth factor receptor; National Medical Products Administration.

Fig. 1

Study design of the ALTER0303 trial. NSCLC, non-small cell lung cancer; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor

Fig. 2

The review process of anlotinib. NDA, new drug application; CMC, chemistry manufacture control; RMP, risk management program

Fig. 3

Kaplan–Meier overall survival curves of patients with advanced non-small cell lung cancer in the anlotinib and place arms