- Anlotinib, a novel multi-targeted tyrosine kinase inhibitor (TKI) developed independently by China, completed a phase III clinical study in advanced non-small cell lung cancer (NSCLC) in 2017 and was approved for marketing on May 9, 2018, for the third-line treatment of patients with NSCLC who have failed or failed to respond to treatment.
- Anlotinib, with its anti-tumor angiogenesis and tumor growth inhibition, not only significantly prolongs patient survival, but also has few toxic side effects and manageable adverse reactions, providing a new option for patients with advanced NSCLC who have progressed after receiving at least second-line therapy in the past.
Anlotinib effectively inhibits kinases such as vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and c-Kit, combining the two main effects of anti-tumor angiogenesis and tumor growth inhibition.
In this article, we discuss the latest research progress of anlotinib in the treatment of NSCLC, including information on the target population, dosing regimen, efficacy, and safety.
Phase II study: anlotinib significantly prolongs survival in advanced NSCLC, with a trend toward longer overall survival
On February 13, 2018, a phase II clinical study, code-named ALTER0302, was officially published in the British Journal of Cancer. The study included patients with advanced NSCLC who had progressed after receiving at least two prior systemic chemotherapies, or who were intolerant.
The results showed that patients in the anlotinib group (4.8 months) had significantly better progression-free survival (PFS) than the placebo group (1.2 months). Also, there was a trend toward longer median survival (mOS) for patients in the anlotinib group (9.3 months) compared with the placebo group (6.3 months).
As for adverse reactions, the most common treatment-related serious adverse reactions to anlotinib included hypertension, elevated thyroglobulin, and hand-foot syndrome. However, after dose adjustment or symptomatic management, all adverse reactions resolved and no treatment-related fatalities occurred.
Phase III study: anlotinib’s efficacy in treated advanced NSCLC validated again, with adverse effects of concern
ALTER 0303 (NCT02388919) is a phase III study evaluating the efficacy and safety of anlotinib in patients with stage IIIB/IV NSCLC who have experienced disease progression after at least second-line therapy. The results showed that anlotinib significantly prolonged the median overall survival of patients by up to 3.33 months compared to placebo. This result reaffirmed the effectiveness of anlotinib in third and later lines for the treatment of advanced NSCLC. And, both patients with adenocarcinoma and squamous carcinoma benefited from anlotinib treatment.
As seen in the subgroup analysis of the ALTER 0303 study, the main adverse events with anlotinib in squamous cancer were hypertension, decreased lymphocyte count, hyponatremia, hemoptysis, and prolonged Q-T interval. Overall, however, the incidence of adverse events was within clinical control and the drug was safe.
Based on the results of these two clinical studies, anlotinib was successfully approved for marketing on May 9, 2018, as a third-line treatment for NSCLC that has failed, or failed, to work with existing therapy.
Progress in the study of different indications of anlotinib
At present, the only approved indication for anlotinib is third-line therapy for advanced NSCLC, but clinical studies are gradually being conducted in small cell lung cancer and other types of tumors based on its multi-targeted nature, demonstrated efficacy, and safety profile.