Tucatinib Plus Trastuzumab Showed Promise Among Patients With HER2-Positive Metastatic Biliary Tract Cancer

Tucatinib plus trastuzumab treatment demonstrated clinically significant antitumor activity and was well-tolerated among patients with previously-treated, HER2-positive metastatic breast cancer, according to results from a phase 2 study.

Yoshiaki Nakamura, MD, National Cancer Center Hospital East, Kashiwa, Japan, and coauthors explained that patients with metastatic biliary tract cancer “that progresses on first-line therapy need well-tolerated treatment options with higher efficacy” than what is currently available. They also noted, “preclinical data have shown that tucatinib and trastuzumab in various HER2[-positive] tumor types results in superior antitumor activity compared with either agent alone.” Results from the phase 2 MOUNTAINEER study evaluating tucatinib and trastuzumab among patients with HER2-positive metastatic colorectal cancer, they wrote, suggest that this combination “may have clinical activity in other HER2[-positive] solid tumors.”

SGNTUC-019 is an open-label phase 2 basket study investigating tucatinib plus trastuzumab for patients with HER2-altered solid tumors. The biliary tract cancer cohort enrolled 30 with HER2 overexpressing or amplified (HER2-positive) tumors who had been previously treated but had not received any prior HER2-directed therapy. Patients received 300 mg tucatinib twice daily and 8 mg/kg trastuzumab then 6 mg/kg every 3 weeks in a 21-day cycle. The primary end point of the study was confirmed objective response rate (ORR).

At the data cutoff date of January 30, 2023, the median duration of follow-up was 10.8 months. The confirmed ORR was 46.7% with a disease control rate of 76.7%. There were 21 patients whose tumors reduced in size. The progression-free survival was 5.5 months, and the estimated 12-month overall survival rate was 53.6%. The time to first response was 2.1 months and the median duration of response was 6 months.

There were 18 patients with grade ≥3 treatment emergent adverse events, generally considered not to be treatment-related. The most common grade ≥3 adverse events were nausea, decreased appetite, and cholangitis. There were 13 patients with serious treatment emergent adverse events, 3 related to tucatinib and 2 to trastuzumab. Study authors noted that 3 patients discontinued tucatinib due to adverse events (cholangitis, interstitial lung disease, liver disorder), while 1 patient discontinued trastuzumab due to interstitial lung disease. All deaths that occurred at the time of the data cutoff (n = 15, 50%) were due to disease progression.

Dr Nakamura et al concluded the results of this study “indicate that tucatinib and trastuzumab appear effective in patients with previously treated HER2[-positive metastatic biliary tract cancer], and clinical activity was observed in patients with IHC 3+ or 2+ tumors.” They added, “the exploratory biomarker analyses demonstrated that multiple HER2 testing methods can be used to help identify patients with HER2[-positive metastatic biliary tract cancer] who may respond to the treatment regimen.”

Journal of Clinical Oncology associate editor Andrew H. Ko, MD, University of California, San Francisco, California, added, “The promising results from this study, while requiring confirmation in larger cohorts, suggest that the combination of tucatinib and trastuzumab may become a useful therapeutic strategy for the subset of patients with HER2[-positive] disease.”

Source:

Nakamura Y, Mizuno N, Sunakawa Y, et al. Tucatinib and trastuzumab for previously treated human epidermal growth factor receptor 2-positive metastatic biliary tract cancer (SGNTUC-019): A phase II basket study. J Clin Oncol. Published online September 26, 2023.