Han B, et al. - Researchers assessed whether anlotinib (a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling) is effective in terms of overall survival of patients with advanced non–small cell lung cancer (NSCLC) progressing after second-line or further treatment, as well as its safety in these patients. With good tolerability, anlotinib showed utility as a potential third-line or further therapy for patients with advanced NSCLC as it appeared to offer prolonged overall survival and progression-free survival among the Chinese NSCLC patients in this trial.

Methods

• Researchers performed the ALTER 0303 trial, which was a multicenter, double-blind, phase 3 randomized clinical trial, in which patients from 31 grade-A tertiary hospitals in China were enrolled between March 1, 2015 and August 31, 2016.
• Eligible subjects were those aged 18 to 75 years who had histologically or cytologically confirmed NSCLC (n=606), and excluded subjects were those who had centrally located squamous cell carcinoma with cavitary features or brain metastases that were uncontrolled or controlled for less than 2 months.
• They randomly assigned patients (n=440), in a 2-to-1 ratio, to receive either 12 mg/d of anlotinib or a matched placebo.
• They treated all cases with study drugs at least once in accordance with the intention-to-treat principle.
• Overall survival was primary end point and the secondary end points were progression-free survival, objective response rate, disease control rate, quality of life, and safety.

Results

• A total of 439 patients were randomized.
• Of those, 296 were randomized to the anlotinib group (106 [36.1%] were female and 188 [64.0%] were male, with a mean [SD] age of 57.9 [9.1] years) and 143 to the placebo group (46 [32.2%] were female and 97 [67.8%] were male, with a mean [SD] age of 56.8 [9.1] years).
• They observed significantly longer overall survival in the anlotinib group (median, 9.6 months; 95% CI, 8.2-10.6) vs the placebo group (median, 6.3 months; 95% CI, 5.0-8.1), with a hazard ratio (HR) of 0.68 (95% CI, 0.54-0.87; P=.002).
• The anlotinib group vs the placebo group had a substantial increase in progression-free survival (median, 5.4 months [95% CI, 4.4-5.6] vs 1.4 months [95% CI, 1.1-1.5]; HR, 0.25 [95% CI, 0.19-0.31]; P < .001).
• Findings revealed considerable improvement in objective response rate and disease control rate in the anlotinib group over the placebo group.