Anlotinib in combination with docetaxel for advanced nonsmall cell lung cancer after failure of platinum-based treatment: A phase 1/2 trial.

Abstract

The combination of anlotinib with chemotherapy has demonstrated encouraging efficacy in the treatment of nonsmall cell lung cancer (NSCLC). The objective of this phase 1/2 trial was to establish the maximum tolerated dose of anlotinib in combination with docetaxel and to assess the efficacy and safety of this regimen in patients with advanced NSCLC who had progressed after platinum-based chemotherapy. In the phase 1 trial, eight patients were enrolled to determine the maximum tolerated dose, which was identified as 10 mg for anlotinib in combination with docetaxel. In the phase 2 trial, in total, 88 patients were randomized, with 57 receiving anlotinib at the established maximum tolerated dose alongside docetaxel and 31 receiving docetaxel monotherapy. Tumor response was evaluated in 88 patients. In the phase 2 study, the combination of anlotinib and docetaxel demonstrated a significant improvement in progression-free survival compared with docetaxel monotherapy (median, 5.39 vs. 2.56 months; hazard ratio, 0.36; 95% confidence interval, 0.21-0.63; p = .0002). The objective response rate was also superior in the combination group (26.32% vs. 6.45%). The median overall survival was 16.82 months for the combination group versus 9.86 months for the monotherapy group (hazard ratio, 0.89; 95% confidence interval, 0.47-1.66; p = .7114). Safety analysis included 96 patients, and the most frequent treatment-emergent adverse events were decreased neutrophil count and decreased white blood cell count. The addition of anlotinib to docetaxel was characterized by a manageable safety profile and also resulted in a significant improvement in progression-free survival among patients with advanced NSCLC who had previously failed platinum-based chemotherapy (ClinicalTrials.gov identifier NCT03726736).