Dr Hays on Unmet Needs in CRC

John L. Hays, MD, PhD, assistant professor, Department of Internal Medicine, The Ohio State University, member, Translational Therapeutics Program, The Ohio State University Comprehensive Cancer Center – James, discusses unmet needs for patients with colorectal cancer (CRC) and future directions for research in this disease.

The optimal way to integrate surgery, radiation, and systemic therapy for patients with CRC has yet to be identified, signaling an unmet need in this disease. Hays says. Although data support the use of upfront chemotherapy or systemic therapy in patients with oligometastatic CRC, many patients with CRC will receive several treatment modalities throughout their disease. These may includetargeted therapies, local therapies such as surgery and radiation, and pseudo-local therapies such as Yttrium-90 treatment or hepatic arterial fusion pumps for patients with liver disease, Hays explains. The roles of each of these treatment options within the overall context of the CRC armamentarium remain unknown and should be defined in the future, Hays notes.

Although sequencing parameters are unclear, the unprecedented variety of approaches for CRC management provides patients with several effective treatment options, Hays emphasizes. However, further research should focus on translating the best options and sequences into clinical practice, according to Hays.

The development of immunotherapy may also benefit patients with CRC, Hays says. For instance, patients with mismatch repair–deficient (dMMR) disease have responded well to treatment with immune checkpoint inhibitors, Hays explains. A phase 2 trial (NCT04165772) evaluated the efficacy of the PD-1 inhibitor dostarlimab-gxly (Jemperli) in patients with stage II or III dMMR rectal cancer. In this trial, all 12 patients (100%; 95% CI, 74%-100%) who completed dostarlimab treatment and underwent 6 or more months of follow-up achieved a clinical complete response.

However, the efficacy of immune checkpoint inhibition appears to be localized to patients with dMMR CRC and is not effective in most patients with mismatch repair–proficient (pMMR) disease, Hays emphasizes. Future research should investigate optimal strategies for harnessing the immune system to target tumor cells in the large population of patients with pMMR CRC. The use of cellular therapies or targeted therapies in combination with immunotherapy may be one such approach, Hays concludes.