Summary

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• Tucatinib (Tukysa) is indicated in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases. It is also used to treat RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following specific chemotherapy treatments.
• Five systematic reviews/meta-analyses provided information on the safety and effectiveness of tucatinib compared to drugs such as lapatinib, pyrotinib, afatinib, and trastuzumab-deruxtecan (T-DXd).
• Studies indicated that tucatinib potentially offers improved survival outcomes for patients with HER2-positive breast cancer brain metastases when combined with capecitabine. The adverse events, including diarrhea, neutropenia, hepatic toxicity, and sensory neuropathy, were considered tolerable compared to other tyrosine kinase inhibitors.
• Compared to lapatinib, pyrotinib, and afatinib, tucatinib showed significant potential in improving progression-free survival in patients with brain metastases according to sensitivity analysis results.
• Tucatinib was superior to other therapies like TDM1 monotherapy, neratinib plus capecitabine, and traditional options such as lapatinib, based on surface under the cumulative ranking (SUCRA) rankings, suggesting its prominence over others.
• The population types include adults who have received one or more prior anti-HER2-based regimens in the metastatic setting, while subgroup considerations focus on those with brain metastases, where it shows promise due to its objective response rate among various treatments.