Dr Li on the Evolution of HER2-Targeted Therapy in HER2+ CRC

Daneng Li, MD, associate professor, Department of Medical Oncology & Therapeutics Research, co-director, Neuroendocrine Tumor Program, City of Hope, discusses the evolution of treating patients with HER2-positive colorectal cancer (CRC) and highlights the effects of implementing HER2-targeted therapy in this patient population.

HER2-targeted therapy has evolved with the addition of new therapies and further research, and has helped propel the CRC treatment armamentarium forward, Li begins. For example, at the advent of HER2-targeted therapy in CRC, treating oncologists only had trastuzumab (Herceptin) to treat patients with, he says. Now, the landscape has evolved to include an additional 8 agents and combination regimens. For instance, tucatinib (Tukysa) in combination with trastuzumab was approved by the FDA on January 19, 2023, in patients with RASwild-type, HER2-positive unresectable or metastatic CRC. In addition, on August 31, 2023, the FDA granted breakthrough therapy designation to fam-trastuzumab deruxtecan-nxki (Enhertu) for patients with unresectable or metastatic HER2-positive solid tumors, including CRC, Li explains. Li believes that these therapies help oncologists produce encouraging responses in patients with CRC, Li adds.

Several questions remain in terms of the potential ideal sequencing of HER2-targeted treatments moving forward, Li expands. Notably, Li shares that research opportunities may arise, including in the first-line setting, to combine HER2-targeted therapies with chemotherapy, Li says. Oftentimes, in patients who have limited disease, oncologists try to elicit as high of an objective response as possible with available therapies so they can potentially downstage those patients’ disease, he emphasizes.

In patients with CRC, even those with stage IV disease, if the oncologist can decrease the number of lesions tolimit the amount of remaining tumor, their disease is potentially still curable, Li continues. Overall, HER2-targeted therapies should be further investigated to better understand whether these agents in combination with chemotherapy can heighten response rates in the first-line treatment setting, Li concludes.