An update on the use of immunotherapy in patients with colorectal cancer.

Introduction: Colorectal cancer (CRC) is the third most common malignancy worldwide, with recent trends demonstrating increasing incidence amongst younger patients. Despite multiple treatment options, metastatic disease remains incurable. A new therapeutic strategy to harness the host immune system, specifically with immune checkpoint inhibitors, now has reported results from a number of clinical trials. Areas covered: This review will discuss in detail microsatellite instability (MSI) and other biomarkers for response to immunotherapy, summarize the pivotal clinical trials of immune checkpoint inhibitors in early-stage and metastatic MSI colorectal cancer, explore strategies to induce treatment responses in MSS CRC and highlight the emerging treatments and novel immune-based therapies under investigation. Expert opinion: Immunotherapy is now a standard of care for the proportion of CRC patients with MSI. While overall survival data are still awaited, the promise of profound and durable responses is highly anticipated. The lack of efficacy in MSS CRC is disappointing and strategies to convert these 'cold' tumors are needed. Further elucidation of optimal use of treatment sequences, combinations and novel agents will improve outcomes.

Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects.

Despite advances, patients with metastatic colorectal cancer (mCRC) still have poor long-term survival. Identification of molecular subtypes is important to guide therapy through standard treatment pathways and holds promise for the development of new treatments. Following standard first- and second-line chemotherapy plus targeted agents, many patients retain a reasonable performance status, and thus are seeking further effective treatment to extend life and maintain symptom control. The challenge lies in selecting the most appropriate therapy in the third- and fourth-line settings, from a range of options including the relatively new oral agents TAS-102 and regorafenib, or rechallenge with previous chemotherapy or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAB). Beyond this, therapy consists of trials involving novel agents and new combinations of treatments with theoretical synergy and/or non-overlapping toxicity. There is a great focus on enhancing immunogenicity in mCRC, to reflect the impressive results of immunotherapy drugs in the small cohort with mismatch repair deficient (dMMR) mCRC. Rare molecular subtypes of mCRC are increasingly being identified, including Her2-positive disease, NTRK fusions and others. Clinical trials exploring the efficacy of immunomodulatory and precision agents are plentiful and will hopefully yield clinically meaningful results that can be rapidly translated into routine care.