Dr Muslimani on the Implications of the MOUNTAINEER Trial in HER2+ mCRC

Alaa Muslimani, MD, oncologist and hematologist, Hematology and Medical Oncology, Atrium Health Levine Cancer Institute, discusses the unmet needs for patients with HER2-positve metastatic colorectal cancer (mCRC) and highlights the implications of the phase 2 MOUNTAINEER trial (NCT03043313) in this patient population.

HER2-positive disease accounts for approximately 2% to 5% of the CRC population, Muslimani begins, adding that HER2-positivity is typically associated with a worse prognosis, and these patients are also resistant to EGFR antibody treatments. In the past, few trials specifically evaluated treatments for patients in the HER2-positive CRC subgroup this disease, and only studied a very small number of patients with the disease, Muslimani notes. Previously, there was no standard of care for how to treat this patient population, Muslimani explains.

However, in January 2023, the FDA granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab (Herceptin) for adult patients with RAS wild-type, HER2-positive unresectable or metastatic CRCthat has progressed after treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. The approval was based on data from the phase 2 MOUNTAINEER trial, which was the largest trial thus far for patients with HER2-positive CRC, Muslimani says. He notes that tucatinib has been effective in the treatment of other type of HER2-positive solid tumors, such as breast cancer.

Now, the National Comprehensive Cancer Network® guidelines include tucatinib plus trastuzumab as a second-line treatment option for HER2-positive mCRC. However, there is no first-line therapy that is FDA approved in the United States for the HER2-positive population, Muslimani notes.

Notably, the ongoing, global, randomized phase 3 MOUNTAINEER-03 trial (NCT05253651) is evaluating tucatinib in combination with trastuzumab and mFOLFOX6 (leucovorin calcium, fluorouracil, and oxaliplatin) vs standard of care as first-line treatment for patients with HER2-positive metastatic CRC.