Targeted Drug Anlotinib Prolongs Survival in Recurrent Small Cell Lung Cancer

Developed in China as a multitargeted tyrosine kinase inhibitor, anlotinib , a drug studied for small cell lung cancer , showed a survival contribution at the ESMO 2019 Congressthrough the ALTER 1202 study.

Approximately 15% of all lung cancers are small cell, generally tending to proliferate/spread faster and recur more often. Until 2018, no cancer drug besides chemotherapy was approved for this disease; within the past 2 years, 3 different immunotherapy drugs received FDA approval: in August 2018, nivolumab (2nd line); in March 2019, atezolizumab (1st line); and in June 2019, pembrolizumab (3rd line). However, for small cell lung cancer, no targeted cancer treatment has entered use to date.

Anlotinib, a small-molecule oral targeted anticancer agent in the “multitargeted angiokinase inhibitor” class, was tested in 120 small cell lung cancer patients in a randomized, phase II, double-blind Chinese study, ALTER 1202.

Patients whose cancer had progressed after at least 2 previous treatment lines were enrolled. In the final analysis, anlotinib, compared with placebo , provided an overall survival advantage: 7.3 months versus 4.9 months.

This benefit was particularly clear in brain metastasis patients (6.3 versus 2.6 months) and those receiving third-line anlotinib (7.3 versus 4.9 months).

These findings appear potentially practice-changing in China, where anlotinib was developed. Seeing activity of this antiangiogenic (new blood vessel-inhibiting) drug in patients with brain metastases is exciting.

After these positive results, trials combining anlotinib with other anticancer drugs were immediately planned, even in second and first lines. How to incorporate it into current approaches and newly approved immunotherapies remains important.

Identifying a biomarker to predict which small cell cancer patients will benefit would also help tailor its use.

Another notable anlotinib study was published at ESMO 2018. The ALTER0203 phase-2B trial involved soft tissue sarcoma and reported a significant survival contribution.

In conclusion, an international phase-3 trial is needed to confirm anlotinib efficacy in small cell lung cancer. Nevertheless, ALTER 1202 not only shows a survival benefit for third-line anlotinib but highlights its magnitude. 

How Does Anlotinib Work?

The following figure shows the small molecule anlotinib and the intracellular tyrosine kinase receptors through which it inhibits new blood vessel formation, cell growth and proliferation.