Tucatinib Plus Trastuzumab Yields Long-Lasting Responses in Previously Treated HER2+ Metastatic CRC

Patients with previously treated HER2-positive metastatic colorectal cancer experienced durable responses following treatment with tucatinib in combination with trastuzumab.

Treatment with a combination of tucatinib (Tukysa) and trastuzumab (Herceptin) resulted in long-lasting responses and a tolerable safety profile in patients with previously treated HER2-positive metastatic colorectal cancer (mCRC), according to a press release from Seagen Inc. detailing topline findings from the phase 2 MOUNTAINEER trial (NCT03043313).

Data from the study, which were presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer, highlighted a confirmed objective response rate (ORR) by blinded independent central review (BICR) of 38.1% (95% CI, 27.7%-49.3%) in those with HER2-positive disease who received the combination at a median follow up or 20.7 months (n = 84). The median duration of response by BICR in this population was 12.4 months (95% CI, 8.5-20.5). Moreover, median progression-free survival (PFS) and overall survival (OS) by BICR were 8.2 months (95% CI, 4.2-10.3) and 24.1 months (95% CI, 20.3-36.7), respectively.

Treatment with single-agent tucatinib (n = 30) resulted in a ORR per BICR by 12 weeks of 3.3% (95% CI, 0.1%-34.9%) and a disease control rate of 80.0%. The trial allowed for crossover to the combination regimen for those treated with tucatinib monotherapy who did not respond or progressed.

“Patients with chemotherapy-refractory HER2-positive metastatic colorectal cancer receive limited clinical benefit with currently available therapies,” lead investigator John H. Strickler, MD, associate professor of medicine at Duke University School of Medicine, said in the press release. “With sustained responses and favorable tolerability in heavily pretreated patients, tucatinib in combination with trastuzumab has the potential to be a new treatment option for previously treated HER2-positive mCRC.”

Patients who were treated with the combination regimen had a median age of 55.0 years. It was reported that at study entry, 64.3% of patients had liver metastases and 70.2% had lung metastases. Moreover, patients had received a median of 3.0 previous lines of systemic therapy.

Patients were treated with either oral tucatinib twice daily on days 1 to 21 and trastuzumab intravenously on day 1 or the tucatinib monotherapy alone. The study’s primary outcome was confirmed ORR, with secondary outcomes including ORR at 12 weeks, DOR, PFS, and OS.

The most frequent grade 1/2 treatment-emergent adverse effects (TEAEs) occurring in 20% or more of those in the combination arm were diarrhea (60.5%), fatigue (41.9%), nausea (34.9%), and infusion-related reactions, and common grade 3 or higher AEs included hypertension (7.0%), diarrhea (3.5%), and fatigue (2.3%). No deaths were attributed to AEs.

“This study has shown the benefits of dual-HER2 inhibition with tucatinib and trastuzumab in patients with HER2-positive metastatic colorectal cancer, including many whose cancer had spread to the liver or lungs before joining the trial,” Roger Dansey, MD, interim chief executive officer and chief medical officer at Seagen, concluded. “We believe this chemotherapy-free combination may play an important role in addressing the unmet needs of patients with this disease.”


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