Tucatinib Plus Trastuzumab Yields Clinically Meaningful Antitumor Activity in HER2-Positive Metastatic Colorectal Cancer

John Strickler, MD, Duke Cancer Institute, Durham, NC, discusses results from the primary analysis of the phase 2 MOUNTAINEER trial, which demonstrated clinically meaningful antitumor activity including durable responses and a median overall survival of 2 years with tucatinib plus trastuzumab for patients with HER2-positive metastatic colorectal cancer.

Tucatinib combined with trastuzumab has the potential to become a new standard of care for this patient population.

Dr Strickler presented these findings at the 2022 ESMO World Congress on Gastrointestinal Cancer in Barcelona, Spain.

Transcript:

I'm John Strickler from Duke University Medical Center in Durham, North Carolina in the United States and I'm here to talk about the MOUNTAINEER Trial, which is presented here at the ESMO World Congress on Gastrointestinal Cancer.

HER2 amplification is present in about 3% of patients with metastatic colorectal cancer and up to 10% of patients with RAS and BRAF wild-type disease. In this study, we explored a novel combination of tucatinib, an oral, highly selective anti-HER2 tyrosine kinase inhibitor together with trastuzumab in patients with HER2-positive metastatic colorectal cancer. This study consisted of three cohorts. Cohort A was launched years ago and the preliminary results of that cohort were shown at the ESMO World Congress in 2019. Based on promising activity demonstrated in that cohort, the study was further expanded. Patients were randomized to Cohort B, which was the tucatinib/trastuzumab combination, or tucatinib monotherapy. Patients who had not responded to tucatinib monotherapy were allowed to cross over to the combination.

In this study, we found that the tucatinib/trastuzumab combination had meaningful anti-tumor activity. We saw a response rate of 38% by blinded independent central review. That was 43% by investigator assessment. We also saw clinically meaningful progression-free survival and overall survival benefit. Overall, the regimen was very well tolerated. There were no treatment-related deaths. Based on these results, this regimen of tucatinib and trastuzumab has the potential to become a new standard of care in patients with chemotherapy-refractory RAS wild-type HER2-positive metastatic colorectal cancer.

Additionally, these results provide rationale to bring tucatinib/trastuzumab into earlier lines of therapy. Based on these results, the MOUNTAINEER-03 trial was recently launched and this study will look at the tucatinib/trastuzumab combination together with FOLFOX against standard of care for patients with first-line, metastatic RAS wild-type HER2-positive colorectal cancer.

Source:

Strickler J, Cercek A, Siena S, et al. Primary analysis of MOUNTAINEER: A phase 2 study of tucatinib and trastuzumab for HER2-positive mCRC. Presented at: ESMO World Congress on Gastrointestinal Cancer; June 29-July 2, 2022. Barcelona, Spain. Abstract LBA-2.