Nicholas Hornstein, Assistant Professor at Northwell Health, shared a post on X about a recent article by John H. Strickler, et al. published in Nature:
“Final analysis of MOUNTAINEER and it’s worth pausing on how big this really was for colorectal cancer
Before this study, HER2 in CRC was interesting biology with very little clinical payoff. MOUNTAINEER changed that.
This was a chemo-refractory, HER2+ RAS WT metastatic CRC population, patients who historically had very few effective options left. A chemotherapy-free, dual HER2 approach with tucatinib plus trastuzumab showed that HER2 is not just present in CRC, it is actionable.
What stood out
- Roughly 4 in 10 patients had meaningful tumor shrinkage
- When responses happened, they were durable, often lasting more than a year
- Disease control was measured in months, not weeks
- Median survival approached two years, something we simply did not see in this setting before
Toxicity pearls and management
- Diarrhea was common, usually early, and very manageable with proactive loperamide and dose adjustments
- Rash was frequent but typically low grade, acneiform in nature, and manageable with topical steroids, doxycycline, and early dermatology involvement when needed
- Fatigue and mild LFT elevations occurred, but serious toxicity was uncommon
- Very few patients discontinued therapy due to side effects and there were no treatment-related deaths
Two other things matter here. First, benefit was seen regardless of how HER2 was identified, tissue or blood, which has real-world implications for testing. Second, the author list is a true who’s who of colorectal cancer, reflecting how much collective effort went into proving this concept.
MOUNTAINEER was the proof-of-principle moment. It showed that HER2 targeting belongs in CRC and laid the foundation for what comes next, including earlier lines of therapy and smarter sequencing.”
Title: Tucatinib plus trastuzumab for chemotherapy-refractory, HER2 + , RAS wild-type metastatic colorectal cancer (MOUNTAINEER): final analysis
Authors: John H. Strickler, Andrea Cercek, Salvatore Siena, Thierry André, Kimmie Ng, Eric Van Cutsem, Christina Wu, Andrew Scott Paulson, Joleen M. Hubbard, Andrew L. Coveler, Christos Fountzilas, Adel Kardosh, Pashtoon Murtaza Kasi, Heinz-Josef Lenz, Kristen Ciombor, Elena Elez, David L. Bajor, Chiara Cremolini, Federico Sanchez, Mina Nayeri, Wentao Feng, Mark Bieda, Tanios S. Bekaii-Saab
Read the Full Article on Nature
More posts featuring Nicholas Hornstein.
