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Dr. Strickler on the Rationale of Examining Tucatinib with Trastuzumab in HER2+ CRC

John H. Strickler, MD, discusses the rationale of tucatinib plus trastuzumab in HER2-positive colorectal cancer.

John H. Strickler, MD, medical oncologist, Duke Cancer Center, Duke Health, discusses the rationale of tucatinib (Tukysa) plus trastuzumab (Herceptin) in HER2-positive colorectal cancer (CRC).

The phase 2 MOUNTAINEER trial (NCT03043313) examined the safety and efficacy of tucatinib in combination with trastuzumab or tucatinib alone in patients with HER2-positive CRC.

Though HER2 is an established actionable target for upper gastrointestinal and breast cancers, it recently emerged as a target in CRC, Strickler says. Next-generation sequencing has allowed for the identification of HER2 amplification in patients with CRC, and it has been observed in approximately 3% of all patients with CRC, Strickler explains. Notably, about 10% of patients with RAS and BRAFwild-type disease also have HER2 amplification, Strickler adds. Despite the identification of HER2 as an actionable biomarker in CRC, there are currently no FDA-approved HER2-targeted therapies for CRC, Strickler explains.

In recent years, data have shown that anti-HER2 therapies are active in HER2-positive tumors outside of breast cancer, Strickler continues. The inception of the MOUNTAINEER trial is to test tucatinib, a highly selective oral anti-HER2 TKI, with trastuzumab, Strickler explains. This began as a pilot study and has expanded to further sites in the United States and Europe, Strickler concludes. 

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