Treating Soft Tissue Sarcoma with the Targeted Medicine Anlotinib

Soft tissue sarcomas originate in supporting tissues called mesenchyme and have many subtypes, forming a rare tumor group. Although they affect people of all ages, the frequency of sarcoma subtypes changes considerably from childhood to adulthood.

Surgery is the main treatment for sarcomas, with chemotherapy and / or radiotherapy potentially added. Few approved treatment options exist for these rare soft tissue cancers. Some subgroups respond little or not at all to chemotherapy, while others respond better; responses to radiotherapy also vary. Over the past twenty years, molecularly targeted medicines and immunotherapies transforming treatment of many cancers have so far shown limited efficacy in sarcomas. Indeed, only 2 targeted medicines [olaratumab (Lartuvo) and pazopanib (Votrient)] have, for sarcomas, FDA approval, while no immunotherapyhas yet been approved for sarcoma treatment.

In the figure below, some soft tissue sarcoma subtypes can be seen.

A Promising New Molecularly Targeted Tyrosine Kinase Inhibitor in Sarcoma Treatment: Anlotinib

As a single medicine, anlotinibwas evaluated for efficacy in ALTER0203 , a phase-2B clinical trial whose results at the ESMO 2018 Congresswere presented as a poster. The primary endpoint was progression-free survival (the duration treatment keeps disease under control). Relationships between anlotinib's efficacy in advanced soft tissue sarcoma and patient age, number of prior treatment lines and dose reductions were also evaluated.

Study Results

• In ALTER0203, 158 patients received anlotinib. Patients with alveolar soft part sarcoma and clear cell sarcoma, totaling 20, had received no prior treatment; 84 had received 1 prior chemotherapy line, and 54 had received at least 2 prior treatment lines.
• Median progression-free survival was similar when patients with no prior treatment or 1 prior line were compared with those receiving at least 2 prior lines (6.7 versus 6.3 months).
• Comparing patients younger than 65 with those aged 65 and older, median progression-free survival with anlotinib was again similar (6.3 and 5.9 months, respectively).
• There was a marked difference in median progression-free survival between patients whose anlotinib dose was reduced at least 1 time during treatment and those without dose reduction: 10.4 months with reduction versus 5.7 months without. Dose reduction of cancer medicines is performed when adverse effects occur. For anlotinib, the occurrence of adverse effects appears also to indicate the medicine's anticancer effect.

In conclusion, Patients requiring dose reduction at least 1 time had longer survival, and anlotinib was effective regardless of prior treatment lines or age. Anlotinib therefore appears to be a targeted medicine with a high likelihood of future approval for soft tissue sarcoma. Phase-3 clinical trial results will determine whether this anticancer small molecule in the tyrosine kinase inhibitor class enters sarcoma treatment practice.

What Is Anlotinib's Mechanism of Action?

In the figure below, the small molecule anlotinib is shown acting within the cell through tyrosine kinase receptors to inhibit cell growth and proliferation.