Medical treatment of advanced chordomas

Chordoma is a very rare bone sarcoma that can arise from any site along the spine and from the skull base. En bloc resection is the gold standard for treatment while radiation therapy has been shown to provide both curative and palliative benefit. Unfortunately, local recurrences are common, even after a complete surgical resection, and up to 40% of patients suffer from distant metastases, while salvage treatments are challenging. Patients carrying an advanced disease need a systemic treatment. Unluckily, conventional chordoma are insensitive to cytotoxic chemotherapy that is considered the standard treatment option in patients with metastatic sarcoma. In the last decade, innovative therapies have been introduced, positively impacting disease control and patients' quality of life. In addition, a better understanding of the molecular characteristics of chordoma allowed to detect new potential targets. This review is focused on the pharmacological management of patients affected by an advanced disease, starting with a summary of data available on conventional chemotherapy, then moving to a deeper analysis of available data on molecular agents and immunotherapy, and finally providing an update on ongoing clinical trials and future prospective.