Cabazitaxel Plus Lapatinib as Therapy for HER2+ Metastatic Breast Cancer With Intracranial Metastases: Results of a Dose-finding Study

Abstract Background Lapatinib is an oral small molecule tyrosine kinase epidermal growth factor receptor-1/HER2 inhibitor that crosses the blood–brain barrier and is active against central nervous system (CNS) metastases. Cabazitaxel is a taxoid that is effective against taxane-resistant metastatic breast cancer (MBC) and has distinguished itself by its ability to cross the blood–brain barrier. The present phase II study ( ClinicalTrials.gov identifier, NCT01934894 ) evaluated the combination of these agents to treat HER2 + MBC patients with CNS metastases. Materials and Methods Patients with HER2 + MBC and ≥ 1 untreated or progressive, measurable CNS metastasis were eligible. Using a 3+3 dose escalation design, patients were treated with escalating doses of intravenous cabazitaxel every 21 days and oral lapatinib daily in 21-day treatment cycles. Intracranial disease restaging was performed every 2 cycles for the first 8 cycles and then every 3 cycles until progression or unacceptable toxicity. Results Eleven patients were treated at 2 dose levels. Six patients were treated at dose level 1 (intravenous cabazitaxel 20 mg/m 2 plus oral lapatinib 1000 mg daily), and five were treated at dose level 2 (intravenous cabazitaxel 25 mg/m 2 plus oral lapatinib 1000 mg daily). The most common treatment-related adverse events were myelosuppression, diarrhea, fatigue, and skin toxicity. A total of 5 dose-limiting toxicity events occurred. No intra- or extracranial objective responses were observed. Conclusion The combination of cabazitaxel plus lapatinib was not feasible because of toxicity and because no objective CNS activity was seen in the 5 evaluable patients. The role of cabazitaxel to treat breast cancer patients with CNS metastases remains undefined.