Tucatinib in patients with HER2-positive advanced/metastatic breast cancer: a systematic literature review of real-world evidence

Background Recent years have seen rapid advances in human epidermal growth factor receptor 2 (HER2)-directed therapies for breast cancer. The shifting therapeutic landscape has presented patients and clinicians with a plethora of effective treatment options, but optimal treatment sequencing can be challenging. Tucatinib is a HER2-selective tyrosine kinase inhibitor that, when given in combination with trastuzumab and capecitabine, has demonstrated survival benefits for patients with HER2-positive (HER2+) metastatic breast cancer (MBC) pretreated with trastuzumab, pertuzumab and trastuzumab-emtansine. Real-world data, which can supplement knowledge gained from clinical trials, has begun to emerge for tucatinib, but a comprehensive review of these studies has yet to be conducted. Methods A systematic literature review was conducted to identify studies published between January 2020 and January 2025 that evaluated the effectiveness and safety of tucatinib in routine clinical practice. Studies were eligible for inclusion if they utilized real-world data, involved patients with HER2+ MBC treated with tucatinib in any line of metastatic therapy, and assessed tucatinib's effectiveness, health-related quality of life (QoL), patient-reported outcomes (PROs), or safety. Results Of 468 unique references identified, 12 publications met the inclusion criteria, 3 of which were manuscripts and 9 of which were congress abstracts. Included studies were heterogeneous in sample size, the lines of therapy assessed, and outcomes reported. Tucatinib-based treatment outcomes in the post-trastuzumab deruxtecan (T-DXd) setting and for patients with brain metastases were also reported. Despite variability among studies, outcomes were broadly consistent with clinical trial findings. Conclusion Overall, the available real-world evidence supports the clinical effectiveness of tucatinib-based therapies in HER2+ MBC, including heavily pretreated populations, patients with prior exposure to T-DXd, and those with brain metastases. However, gaps remain in the real-world data regarding the safety profile of tucatinib and its impact on health-related quality of life in routine clinical practice.