Dr. Strickler on the Exploration of Frontline Tucatinib/Trastuzumab in HER2+ CRC

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

Data from the phase 2 MOUNTAINEER trial (NCT03043313) showed that tucatinib plus trastuzumab elicited clinically meaningful and durable responses in patients with previously treated metastatic HER2-positive CRC. Now investigators want to explore whether this combination be a viable first-line option for this patient population, Strickler explains.

The ongoing phase 3 MOUNTAINEER-03 trial (NCT05253651) is exploring the combination of tucatinib and trastuzumab plus modified fluoropyrimidine, leucovorin, and oxaliplatin (mFOLFOX6) vs standard of care as a frontline treatment for patients with HER2-positive CRC, Strickler says.

Other ongoing trials are examining anti-HER2 regimens vs anti-EGFR regimens in the second-line setting and beyond to investigate if there is still a role for anti-EGFR therapies in patients with HER2-positive CRC, Strickler adds. Preclinical data have suggested that HER2 expression drives resistance to anti-EGFR therapy, though this has yet to be seen in a prospective, randomized trial, Strickler concludes.