Tanios S. Bekaii-Saab, MD, on Potential of Dual Targeting to Transform Treatment of HER2+ CRC

At 2022 ASCO, Tanio S. Bekaii-Saab, MD, reviews the MOUNTAINEER trial of trastuzumab plus tucatinib for HER2-positive metastatic colorectal cancer and foreshadows how an approved regimen may help improve outcomes in this patient population.

CancerNetwork® spoke with Tanio S. Bekaii-Saab, MD, Gastrointestinal Cancer Program lead at the Mayo Clinic Cancer Center and medical director of the Cancer Clinical Research Office as well as vice chair and section chief for Medical Oncology in the Department of Internal Medicine at the Mayo Clinic in Phoenix, Arizona, about information from the ongoing phase 2 MOUNTAINEER trial (NCT03043313) assessing tucatinib (Tukysa) plus trastuzumab (Herceptin) for patients with metastatic colorectal cancer (CRC) that were made available at the 2022 American Society of Clinical Oncology Annual Meeting. He describes his interest in the combination’s potential to make dual targeting of HER2 a winning strategy for this patient population.1

Later in the month, data from the trial that read out at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer showed that the combination resulted in long-lasting responses and a tolerable safety profile in patients with previously treated HER2-positive metastatic CRC.2


This patient population comprises about 2% to 4% of patients with colorectal cancer. They tend to be KRAS or RAS wild-type overall. That’s a small proportion of patients. The implications for this subgroup of patients is that there may be an [additional] option that’s approved. The good news is we’ve known for a while that this was a valid target and there were smaller studies that suggested dual targeted strategies could technically improve outcomes, [but there has never been] a registration strategy, per se.

What they focused on were NCCN [National Comprehensive Cancer Network] guidelines. There [were small studies or] arms in a basket trial, such as [those examining] trastuzumab and pertuzumab [Perjeta]. This is the only study that was focused just on colon cancer and is large enough and includes a randomized proportion. That is big news because other than the NCCN guidelines and the lower-level evidence, this could lead to an approval. I see this as transformative and will raise awareness about HER2 as a target in colon cancer. This [will be] up to par with gastric cancer and breast cancer as a relevant target with an approved combination if it goes through the FDA.


  1. Strickler JH, Ng K, Cercek A, et al. MOUNTAINEER: open-label, phase II study of tucatinib combined with trastuzumab for HER2-positive metastatic colorectal cancer (SGNTUC-017, trial in progress). J Clin Oncol. 2022;40(suppl 3):TPS153. doi:10.1200/JCO.2022.40.4_suppl.TPS153
  2. Seagen announces results from pivotal MOUNTAINEER trial demonstrating clinically meaningful antitumor activity of TUKYSA® (tucatinib) in combination with trastuzumab in previously treated HER2-positive metastatic colorectal cancer. News release. Seagen Inc. July 2, 2022. Accessed July 6, 2022. https://bit.ly/3utbj9c