Tucatinib With Trastuzumab Shows Positive Effects in Patients With Bile Duct Cancer

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According to results from the SGNTUC-019 (NCT04579380) study presented at the 2024 European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research Symposium in Barcelona, Spain, treatments that are designed to target human epidermal growth factor receptor 2 (HER2)-positive breast cancer are also able to benefit some patients who have bile duct cancer. Bile duct cancer is rare, therefore, treatment options are limited and survival rates are low for patients with the disease.¹

SGNTUC-019 (NCT04579380) is a multi-cohort, open-label, international phase 2 basket study that evaluated the efficacy and safety of tucatinib (Tukysa; Array BioPharma) and trastuzumab (Herceptin; Genentech) in patients with previously treated, HER2+ or HER2-mutated locally advanced or metastatic solid tumors by local or central testing. Patients received 300 mg of tucatinib orally twice per day and 8 mg/kg on day 1 of cycle 1, then 6 mg/kg every 21 days beginning day 1 of cycle 2. Patients were treated in 21-day cycles. According to the investigators, all patients had no prior HER2-directed therapy, except for certain patients in the uterine cancer cohort.^2,3

The primary end point of the study was confirmed objective response rate (cORR), which was assessed from the initiation of treatment and up to about 2 years. Secondary end points included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety end points, all of which were also assessed up to 2 years except for OS.³

For this analysis, a total of 217 patients received tucatinib and trastuzumab, of which 212 had evaluable responses. According to the findings, cORR was approximately 22.2%, and was 22.3% in HER2+ tumors and 21.9% HER2-mutated tumors. In addition, those who had bile duct cancer (n = 30) demonstrated an approximate cORR of 46.7%.^1,2

“This chemotherapy-free combination was shown to be safe and well-tolerated. Very few patients had to stop treatment due to [adverse] effects. The results of the study show variable effects across different tumor types. However, patients with HER2-positive metastatic bile duct cancer and HER2-mutated metastatic breast cancer experienced clinically relevant ORRs,” Yoshiaki Nakamura, MD, PhD, from the National Cancer Center Hospital East in Kashiwa, Japan, said in a news release. “These results support inclusion of this drug combination in guidelines for patients with previously treated HER2-positive bile duct cancer. The results for the patients with metastatic breast cancer suggest that those with HER2-mutated tumors could also benefit from these HER2-targeted treatments.”¹

The most common treatment-emergent adverse effects (TEAEs) observed in the trial were diarrhea (52%) and nausea (31%), with most common grade 3 or higher TEAEs being anemia (9%) and increases in alanine aminotransferase (7%). According to the investigators, few patients discontinued tucatinib (6%) and trastuzumab (5%) because of their TEAEs.^1,2

In addition, a combination of tucatinib, trastuzumab, and the chemotherapy drug capecitabine (Xeloda; Genentech) is currently approved for patients who have metastatic breast cancer that is HER2+. In the new trial of tucatinib and trastuzumab without capecitabine, 31 patients with metastatic HER2-mutated breast cancer demonstrated an approximate ORR of 41.9%. Currently, there are other trials testing tucatinib in combination with other drugs in cancers, such as HER2+ breast and bowel cancers.¹

“…HER2 has been well-studied in breast cancer, but we are starting to see that it could be a useful target for treating other cancers,” Tim Greten, MD, senior investigator at the Center for Cancer Research, said in the news release. “This study suggests that using 2 drugs that both target HER2 could prove beneficial for a wider group of breast cancer patients and for some patients with bile duct cancer. However, this is an early trial, and we need to see further research to confirm these results.”¹

REFERENCES

1. AACR. Treatments used for HER2-positive breast cancers could help patients with rare gastrointestinal cancer. News release. October 24, 2024. Accessed October 28, 2024. https://aacr.ent.box.com/s/nie96nazg21nhg98ty20zq7v4swbhs9y

2. Nakarmura Y, Bekaii-Saab T, Hamilton E, et al. Tucatinib and Trastuzumab for Patients With Previously Treated, HER2-Altered Solid Tumors (SGNTUC-019): A Phase 2 Basket Study. Presented at: European Organisation for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research Symposium; Barcelona, Spain. October 23-25, 2024. https://aacr.ent.box.com/s/9jo4uf8wmgj28d5nhezjaw3fm292faia

3. Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations. ClinicalTrials.gov identifier: NCT04579380. Updated November 18, 2023. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT04579380