(Breast Cancer) Is Tucatinib Plus Trastuzumab Plus Capecitabine Effective?
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Tucatinib + Trastuzumab + Capecitabine in HER2-Positive Breast Cancer
- January 3, 2020
- Reading time: 2 minutes
On October 21, 2019, Seattle Genetics announced positive results from the HER2CLIMB Phase 2 clinical trial: "Efficacy and safety of oral HER2 inhibitor tucatinib plus trastuzumab plus capecitabine in patients with HER2-positive locally advanced or metastatic breast cancer previously treated with trastuzumab, pertuzumab, and ado-trastuzumab emtansine (T-DM1)."
HER2CLIMB Trial Design
HER2CLIMB was an international multicenter, double-blind, placebo-controlled trial. Patients with HER2-positive locally advanced/metastatic breast cancer previously treated with trastuzumab, pertuzumab, and T-DM1 were randomized 2:1 to:
Tucatinib group (21-day cycle): Tucatinib 300 mg twice daily + trastuzumab 6–8 mg/kg on Day 1 + capecitabine 1000 mg/m² twice daily on Days 1–14
Placebo group (21-day cycle): Placebo + trastuzumab 6–8 mg/kg on Day 1 + capecitabine 1000 mg/m² twice daily on Days 1–14
Primary endpoint: progression-free survival (PFS). Secondary endpoints: overall survival (OS) and PFS in patients with brain metastases.
Efficacy Results
- PFS: Tucatinib group showed a 46% reduction in progression risk (HR 0.54) — a significant improvement
- OS: Tucatinib group showed a 34% reduction in death risk (HR 0.66) — a significant improvement
- PFS in brain metastasis patients: 52% reduction in progression risk (HR 0.48) — a significant improvement
Safety Profile
Side effects in the tucatinib group were generally manageable and tolerable. Most common adverse events: diarrhea, hand-foot syndrome, nausea, fatigue, and vomiting.
Grade 3 adverse events:
- Diarrhea: Tucatinib 12.9% / Placebo 8.6%
- AST elevation: Tucatinib 4.5% / Placebo 0.5%
- ALT elevation: Tucatinib 5.4% / Placebo 0.5%
- Treatment discontinuation due to adverse events: Tucatinib 5.7% / Placebo 3.0%
Conclusions
Based on HER2CLIMB results, Roger Dansey concluded: In HER2-positive locally advanced or metastatic breast cancer patients with limited prior treatment options, adding tucatinib to the standard trastuzumab plus capecitabine regimen significantly improved PFS, OS, and PFS in brain metastasis patients. A new drug application was to be submitted in Q1 2020 based on these results.
Tags: #BreastCancer #Tucatinib #Trastuzumab #Herceptin #Capecitabine #Xeloda
- Clinical trial drug
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