Clinical News

Tucatinib plus trastuzumab for RAS wild-type, HER2-positive metastatic colorectal cancer: Results from the phase II MOUNTAINEER trial

2023-02-14 

Abstract: The phase II MOUNTAINEER trial demonstrated statistically significant results of tucatinib and trastuzumab combinations in RAS wild-type, HER2-positive metastatic colorectal cancer who failed with prior chemotherapy.

HER2 amplification or overexpression has been reported in about 3-5% of metastatic colorectal cancer (mCRC). For this group of patients who were treated with standard chemotherapy regimens would have limited useful treatment options afterward. The phase II MOUNTAINEER trial was initiated to evaluate the efficacy of tucatinib, a highly selective HER2 inhibitor, in combination with trastuzumab for RAS wild-type, HER2-positive mCRC patients who have progressed following fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

The result showed an overall response rate (ORR) of 38.1% in the tucatinib plus trastuzumab cohort with a median duration of response of 12.4 months, median progression-free survival of 8.2 months, and median overall survival of 24.1 months. Of note, the ORR by 12 weeks was only 3.3% in the tucatinib monotherapy cohort and for patients who crossed over to the dual HER2 blockade, the ORR was increased to 17.9%. The most common adverse events are diarrhea (64%), fatigue (44.2%), and abdominal pain (15.1%). Based on the results, the U.S. FDA granted accelerated approval on Jan 19, 2023.

In summary, the combination of tucatinib and trastuzumab showed clinical benefit in RAS wild-type, HER2-positive mCRC patients who were treated with standard chemotherapy. In addition, a global phase III MOUNTAINEER-03 trial to evaluate the efficacy of tucatinib, trastuzumab, and mFOLFOX6 combination in first-line setting is ongoing.

Additional analyses of MOUNTAINEER: A phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC (Slide presentation in ESMO 2022)