Tanios S. Bekaii-Saab, MD, Forecasts Treatment Landscape of CRC as More Targeted Regimens Become Available

Tanios S. Bekaii-Saab, MD, discussed how data from clinical trials examining different targeted strategies in colorectal cancer will transform the way in which patients with this malignancy are seen and treated.

Tanios 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 n the Department of Internal Medicine at the Mayo Clinic in Phoenix, Arizona, spoke with CancerNetwork® about his predictions for the future of colorectal cancer (CRC) treatment following presentations from the 2022 American Society of Clinical Oncology Annual Meeting.

Bekaii-Saab and colleagues presented a poster about the ongoing phase 2 MOUNTAINEER trial (NCT03043313) of tucatinib (Tukysa) plus trastuzumab (Herceptin) for patients with metastatic CRC, which he sees as a small piece of the larger precision paradigm.


Right now, the most relevant targets for first-line decisions are MSI [microsatellite instability], BRAF mutations, RAS mutations, and now HER2 amplifications. Most of the stratifying factors are prognostic in the first line and become more predictive for later lines. I foresee 5 years from now, we’re going to be thinking in [terms of] subgroups rather than [treating] larger groups first then worrying about the subgroups as we go down the line of therapy. Ultimately, this is going to become multiple cancers—not just one cancer—with a specific target that you can go after.

It keeps on changing; it’s amazing. In 20 years from when I entered the world of [gastrointestinal] oncology, the options were bolus 5-FU [fluorouracil] or infusion 5-FU, then came irinotecan, then came oxaliplatin, then we started thinking about how to combine the 2, then came bevacizumab [Avastin] for all patients without selection. Then came cetuximab [Erbitux] and panitumumab [Vectibix] for the KRAS wild-type tumors. Then we understood there’s more than just KRAS wild-type [to consider such as] expanded RAS and BRAF mutations that don’t appear to respond. Then we’ve start chipping away [at treating patients] subgroup by subgroup in just the last few years. If you look at survival of patients, we’ve moved from about a year to closer to 3 to 4 years, and now to more than 5 years for some subgroups. It’s amazing, and that has only happened in the last decade.


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