Dr. Messersmith on the Potential for Trastuzumab Deruxtecan in HER2+ CRC

Wells Messersmith, MD, a physician, division head, and associate director for translational research at the University of Colorado School of Medicine, discusses the potential for fam-trastuzumab deruxtecan-nxki (Enhertu) as a treatment for patients with HER2-positive colorectal cancer (CRC).

While trastuzumab deruxtecan was FDA approved in January 2021 for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma, data regarding its efficacy in patients with CRC is still early on, and the agent has not yet been approved in that patient population, Messersmith says. However, larger clinical trials should bring forth data regarding the agent that could lead to an FDA approval, he adds. 

In the phase 2 DESTINY-CRC01 trial (NCT03384940), which is examining the agent in patients with HER2-expressing metastatic CRC, patients had received at least 2 prior lines of treatment for CRC. Moreover, the trial enrolled patients who have RAS wild-type and BRAF wild-type disease and central confirmation of HER2 expression, Messersmith explains. Additionally, the primary end point for this trial is objective response rate (ORR), while progression-free survival and overall survival are being examined as secondary endpoints.

Current later line options for patients with CRC, such as regorafenib (Stivarga) and trifluridine/tipiracil (TAS-102; Lonsurf), have yielded low response rates remain, Messersmith notes. While it will be important to see data from a more extensive cohort, early data have shown that trastuzumab deruxtecan elicited an ORR of 45.3%, making it a promising option for patients with CRC, Messersmith concludes.