Global Perspectives on Treatment of Metastatic Colorectal Cancer - Episode 9

New Agents for Refractory Metastatic Colorectal Cancer

The phase III CONCUR trial confirmed that regorafenib, a multi-kinase inhibitor, improves survival when compared with placebo in patients with previously treated metastatic colorectal cancer (mCRC). In the trial, 38% of patients had received ≥3 previous treatment lines for metastatic disease. Median overall survival was 8.8 months for patients who received regorafenib vs 6.3 months for patients who received placebo (HR, 0.55; P = .00016). Median progression free survival was 3.2 versus 1.7 months, with regorafenib and placebo, respectively (HR, 0.31; P <.0001).

Regorafenib is a very active drug, notes Dirk Arnold, MD, PhD, but the toxicities can be an issue. The drug is associated with severe liver toxicity, fatigue, loss of appetite, mucositis, and elevated blood pressure. Regorafenib can be considered for any refractory patient with good performance status, adds Arnold. It can also be used as part of a maintenance strategy, notes Fortunato Ciardiello, MD, PhD.

Regorafenib should be dosed 160 mg, three weeks on, one week off, although this dose is not appropriate for all patients, states Ciardiello. The dosing is not weight-based. In practice, many clinicians initiate patients on 120 mg and either scale up to 160 or maintain 120 mg. Ongoing clinical trials are exploring a dosing flexibility for the first month of treatment to understand the appropriate dose for the patient.

TAS-102 is an investigational agent for mCRC, which was recently approved in the United States. An application for the agent is still pending in Europe. Clinical trial results have shown that while the medication has been tolerated systemically, it can be highly myelosuppressive. There are still many questions around appropriate sequencing for TAS-102 and regorafenib, notes Arnold.