Optimizing the first-line treatment for metastatic colorectal cancer

Abstract

Colorectal cancer represents an important oncological challenge both for its incidence, which makes it an important health problem, and for its biological complexity, which has made clinical results very difficult in terms of outcome for this category of patients. To date these diseases should not be treated as a single entity but it is necessary to distinguish colorectal cancers based on characteristics that nowadays are essential to have greater therapeutic benefits. These include the sideness of the disease, the state of microsatellites, the presence of prognostic and predictive mutations of response to treatments currently available in clinical practice, which are associated with new therapeutic targets. The greatest challenge in the future will be to circumvent the resistance mechanisms that make this disease very difficult to treat with good long-term results by studying effective combination treatments with a good toxicity profile. Once such combinations or targeted treatments are consolidated, it will be desirable to shift the best therapies to the first line treatment to make them immediately accessible to the patient. It will also be essential to refine the selection of patients who can benefit from these treatments.

Binimetinib in combination with nivolumab or nivolumab and ipilimumab in patients with previously treated microsatellite-stable metastatic colorectal cancer with RAS mutations in an open-label phase 1b/2 study

“…The first in-human trial of binimetinib identified 60 mg twice daily (BID) as the maximum tolerated dose (MTD) and 45 mg BID as the recommended phase 2 dose (RP2D) for binimetinib monotherapy in patients with BRAF-mutant CRC [ 16 ]. Preliminary results indicate that binimetinib treatment in combination with ICIs has encouraging activity and acceptable tolerability in patients with MSS mCRC [ 18 , 19 ].…”