Tucatinib

Researchers successfully demonstrated the feasibility of using real-world data to create an external control arm for a phase 2 trial of tucatinib plus liposomal doxorubicin in HER2-positive breast cancer patients.

• A combination of tucatinib and trastuzumab demonstrated significant efficacy, achieving 42% tumor shrinkage in HER2-negative breast cancer patients with specific HER2 mutations. • The dual HER2-targeted approach represents a potential breakthrough for patients with previously treated breast cancer, offering new hope for those with limited therapeutic options. • This development highlights the growing importance of mutation-specific targeting in breast cancer treatment, potentially expanding the utility of established HER2-directed therapies.

• A phase 2 basket trial (SGNTUC-019) demonstrates the efficacy of tucatinib and trastuzumab, combined with fulvestrant in HR+ cases, in heavily pretreated HER2-mutated metastatic breast cancer (MBC). • The combination therapy achieved a confirmed objective response rate (cORR) of 41.9% and a median duration of response (DOR) of 12.6 months in HER2-mutated MBC patients. • Median progression-free survival (PFS) was 9.5 months, and median overall survival (OS) was 20.1 months, indicating clinically meaningful activity despite extensive prior treatments. • The chemotherapy-free regimen was well-tolerated, with manageable adverse events, supporting further investigation of HER2-directed therapies in this patient population.

• Molecular testing is crucial for mCRC patients to identify eligibility for targeted therapies, including BRAF, HER2, and RAS-directed treatments. • The BEACON regimen, combining encorafenib and cetuximab, has demonstrated clinical utility in BRAF V600E-mutated mCRC after first-line chemotherapy. • The MOUNTAINEER trial's regimen of trastuzumab plus tucatinib is an FDA-approved option for HER2-positive mCRC in the second line. • Antibody-drug conjugates like fam-trastuzumab deruxtecan-nxki (Enhertu) show effectiveness in HER2-high mCRC, even after prior HER2-directed therapy.

• Leading oncologists discuss optimal treatment strategies for HR+/HER2+ metastatic breast cancer, emphasizing THP (docetaxel/paclitaxel, trastuzumab, pertuzumab) as the preferred first-line therapy followed by maintenance treatment. • Experts debate the role of endocrine therapy in combination with HER2-targeted treatments, suggesting potential benefits of adding fulvestrant or aromatase inhibitors after chemotherapy completion. • Site of metastasis emerges as a key consideration in treatment selection, with recent data challenging traditional approaches to brain metastases and expanding options for patients with various metastatic presentations.