Entry Detail
| General information | |
| Database: | DB01052 |
| Objective: | lapatinib plus capecitabine or lapatinib plus topotecan for patients with human epidermal growth factor receptor 2positive breast cancer brain metastases. |
| Authors: | Nancy U. Lin |
| Title: | Randomizedphase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with human epidermal growth factor receptor 2positive breast cancer brain metastases. |
| Journal: | J Neurooncol |
| Year: | 2011 |
| PMID: | 21706359 |
| Trial Design | |
| Clinical Trial Id: | NCT00437073 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | lapatinib plus capecitabine or lapatinib plus topotecan |
| Study Type: | an openlabel, randomizedphase II study. |
| Key Patients Feature: | Eligible patients had human epidermal growth factor receptor 2positive breast cancer (defined as 3+ immunohistochemistry or evidence of gene amplification by fluorescence in situ hybridization) and unequivocal radiographic evidence of new and/or progressive metastases in the brain despite prior standard treatment with WBRT and/or SRS. Prior trastuzumab exposure was also required. Patients had at least one measurable brain lesion (more than and equal to 10 mm on T1 weighted, gadoliniumenhanced magnetic resonance imaging [MRI]). Other eligibility criteria included age more than and equal to 18 years, Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1, life expectancy>12 weeks, cardiac ejection fraction within institutional normal range, ability to swallow and retain oral medications, and adequate organ function. |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | NA |
| Control Group Info: | Lapatinib plus topotecan arm |
| Treatment Info: | Lapatinib plus capecitabine arm received lapatinib 1, 250 mg orally once daily and capecitabine 2, 000 mg/m2 orally divided twice daily on days 1-14 of a 21day cycle. Lapatinib plus topotecan arm received lapatinib 1, 250 mg orally once daily and topotecan 3.2 mg/m2 intravenously on days 1, 8, and 15 of a 28day cycle. |
| Primary End Point: | objective response in the CNS. |
| Secondary End Point: | safety and toxicity profile, percentage ofpatients with disease stabilization more than and equal to 6 months, clinical benefit rate (CR ¡À PR ¡À SD more than and equal to 6 months), duration of CNS objective response, percentage of patients with improvements in NSS, ORR in nonCNS sites, initial site of disease progression, time to progression, and overall survival. |
| Patients Number: | 22 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate (ORR) in the lapatinib plus capecitabine arm was 38% (exact 95% confidence interval [CI] 13.9-68.4) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The combination of lapatinib plus topotecan was not active and was associated with excess toxicity. |
| Conclusions: | the present study provides a promising indication of CNS activity with the combination of lapatinib and capecitabine in patients with refractory brain metastases from human epidermal growth factor receptor 2positive breast cancer. Definitive conclusions cannot be made as the study was stopped prior to full accrual. The combination of lapatinib and topotecan is not recommended given the excess toxicity observed. Ongoing and planned studies are evaluating the activity of lapatinib and other human epidermal growth factor receptor 2targeted agents in patients with previously untreated brain metastases as an alternative to radiotherapy, or for the prevention of brain metastases in patients at high risk. |