Anlotinib is an oral small-molecule drug developed as a targeted therapy for solid tumors. It interferes with specific molecular pathways required for tumor growth and survival. It is utilized in the management of several advanced-stage cancers where other systemic treatments have proven ineffective or are no longer tolerated. Anlotinib offers a new treatment option by targeting the machinery cancer cells use to grow and spread.
Mechanism of Action: Targeting Cancer Growth
Anlotinib is classified as a multi-target receptor tyrosine kinase (RTK) inhibitor, meaning it blocks the activity of several proteins that function as cellular signal switches. Receptor tyrosine kinases are located on the surface of cells and transmit growth signals from outside to the inside of the cell. In many cancers, these switches are stuck in the “on” position, constantly telling the cell to grow and divide uncontrollably.
The drug exerts its anti-cancer effect through two primary mechanisms: inhibiting the cancer cell’s proliferation signals and disrupting the tumor’s blood supply. Anlotinib potently targets vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, which are integral to a process called angiogenesis. Angiogenesis is the formation of new blood vessels that tumors require to deliver oxygen and nutrients for sustained growth, essentially starving the tumor of its lifeline.
Beyond its anti-angiogenic role, Anlotinib also blocks other RTKs, including fibroblast growth factor receptors (FGFR) and platelet-derived growth factor receptors (PDGFR). These receptors are involved in driving cell proliferation, survival, and resistance to other therapies. By simultaneously inhibiting these multiple pathways, Anlotinib provides a broad-spectrum approach to suppressing tumor growth and metastasis.
Approved Therapeutic Uses
The primary approved use of Anlotinib is in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC). It is approved as a third-line or further-line treatment for patients whose disease has progressed following at least two prior lines of systemic therapy. Clinical trials demonstrated a significant improvement in overall survival for patients receiving Anlotinib compared to a placebo in this setting.
Beyond NSCLC, Anlotinib has also received approval for other challenging malignancies. It is indicated for the treatment of soft tissue sarcoma (STS) and has shown benefit in patients with advanced medullary thyroid carcinoma. For small cell lung cancer (SCLC), Anlotinib has been approved as a third-line and above treatment based on improved progression-free survival and disease control rates.
The drug’s broad activity profile has led to its investigation in other cancer types, including renal cell carcinoma and gastric cancer. While NSCLC remains the most established indication, its utility spans various solid tumors. Efficacy is typically measured by its ability to prolong progression-free survival and overall survival compared to standard care or placebo.
Common Adverse Reactions and Management
Since Anlotinib works by inhibiting pathways related to blood vessel function and cell signaling, its side effect profile often reflects this mechanism. Hypertension, or high blood pressure, is one of the most frequently reported adverse events, occurring in a majority of patients. Blood pressure should be closely monitored, and treatment with anti-hypertensive medications is often necessary to manage this side effect, with timely intervention preventing more severe complications.
Another common reaction is hand-foot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, which involves redness, swelling, and pain on the palms and soles. Management strategies for HFS include the use of topical cortisone creams, supportive care, and patient education on avoiding activities that cause friction or heat on the hands and feet. For more severe cases, a temporary interruption or reduction of the Anlotinib dose may be required to allow symptoms to resolve.
Fatigue is a prevalent side effect that can range from mild to severe, impacting a patient’s quality of life. Other notable adverse events include elevated thyroid-stimulating hormone (TSH), which can indicate hypothyroidism, and proteinuria, which is the presence of excess protein in the urine. Thyroid function should be regularly tested, and abnormal TSH levels may be managed with hormone replacement therapy.
The presence of proteinuria can signal potential kidney issues, requiring routine urine tests and monitoring of kidney function. Gastrointestinal issues like diarrhea are also common, typically managed with supportive care, such as anti-diarrheal medications. Dose modification, including reduction or temporary suspension, is employed to manage all adverse reactions while ensuring patient safety.
Global Regulatory Status
Anlotinib has a distinct regulatory history, with its initial and primary approval taking place in China. The drug was first approved by the China National Medical Products Administration (NMPA) in 2018 for the treatment of advanced non-small cell lung cancer that had progressed after two or more lines of prior systemic treatment. Subsequently, the NMPA expanded its approvals to include other indications like soft tissue sarcoma, small cell lung cancer, and medullary thyroid carcinoma.
Its availability is currently concentrated in the Chinese market, where it was developed. In other major global markets, such as the United States (US) and the European Union (EU), Anlotinib does not yet hold broad market approval for its main indications. However, the drug is undergoing extensive international clinical development, with Phase II and Phase III trials being conducted for various cancer types in countries including the US and Italy.
The US Food and Drug Administration (FDA) has previously granted Anlotinib an orphan drug designation for certain rare cancers, such as ovarian cancer. This designation facilitates the development process but does not constitute full marketing approval. Ongoing clinical trials in these regions are necessary to gather the data required to support future regulatory submissions and potential market entry outside of China.