Tukysa Plus Herceptin May Offer ‘Chemotherapy-Free’ Regimen for HER2-Positive Colon Cancer

Tukysa (tucatinib) plus Herceptin (trastuzumab) was well-tolerated and efficacious in treating patients with HER2-positive metastatic colorectal cancer, according to recent findings from the phase 2 MOUNTAINEER clinical trial.

“Patients with chemotherapy-refractory HER2-positive metastatic colorectal cancer receive limited clinical benefit with currently available therapies,” Dr. John H. Strickler, an associate professor of medicine at Duke University School of Medicine in Durham, North Carolina, and lead trial investigator, said in a press release.

Findings, which were recently presented at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer, showed that at an average follow-up of 20.7 months, 38.1% of patients given Tukysa plus Herceptin had a confirmed objective response, meaning that their disease shrunk as a result of treatment. Among these patients, average duration of response was 12.4 months.

Additionally, patients treated with Tukysa and Herceptin lived for an average of 8.2 months before their disease progressed — a metric known as progression-free survival. Average overall survival (time from treatment until death from any cause) was 24.1 months.

A total of 84 patients received the drug duo — 64.3% had liver metastases and 70.2% had lung metastases at the start of treatment. The average prior number of therapies was three and ranged between one and six.

“This study has shown the benefits of dual-HER2 inhibition with (Tukysa) and (Herceptin) in patients with HER2-positive metastatic colorectal cancer, including many whose cancer had spread to the liver or lungs before joining the trial,” Dr. Roger Dansey, the interim CEO and chief medical officer of Seagen, the manufacturer of Tukysa, said in a press release. “We believe this chemotherapy-free combination may play an important role in addressing the unmet needs of patients with this disease.”

The trial also included a group of 30 patients who received only Tukysa. For this group, the overall response rate was 3.3%, with a disease control rate of 80%. Patients whose disease did not respond to Tukysa or who progressed on the single-agent were allowed to switch over to receive treatment with Tukysa and Herceptin in combination.

Tukysa was approved by the Food and Drug Administration to be used in combination with Herceptin and the chemotherapy drug Xeloda (capecitabine) in 2020 for patients with HER2-positive breast cancer.

The most common side effects in patients with HER2-positive metastatic colorectal cancer who received Tukysa plus Herceptin was diarrhea (60.5% grade 1 or 2 and 3.5% grade 3), fatigue (41.9% grade 1 or 2; 2.3% grade 3), nausea (34.9% grade 1 or 2) and infusion-related reaction (20.9% grade 1 or 2). The most common severe (grade 3 or higher) side effect was hypertension (high blood pressure), which occurred in 7% of patients on the two-drug combination.

Of note, a grade 1 or 2 side effect is considered mild or moderate in terms of severity. Anything over grade 3 is considered severe, life-threatening or fatal.

A total of 5.8% of patients had to stop treatment as a result of side effects, and there were no deaths reported.

“With sustained responses and favorable tolerability in heavily pretreated patients, (Tukysa) in combination with (Herceptin) has the potential to be a new treatment option for previously treated HER2-positive (metastatic colorectal cancer),” Strickler said.

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