Entry Detail
| General information | |
| Database: | DB00656 |
| Objective: | It is known that one third of patients with human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2)overexpressing metastatic breast cancer (MBC) treated with trastuzumab will develop brain metastases. As the development of brain metastases is fatal, controlling its progression is clinically meaningful. however, effective therapy for MBC patients with brain metastasis after cranial radiation is limited. The international clinical study in which six Japanese patients participated indicated the antitumor activity of lapatinib against brain metastases of human epidermal growth factor receptor 2overexpressing breast cancer. |
| Authors: | Iwata H, et al |
| Title: | a phase II study of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2overexpressing breast cancer following trastuzumab based systemic therapy and cranial radiotherapy: subset analysis of Japanese patients. |
| Journal: | Int J Clin Oncol. |
| Year: | 2013 |
| PMID: | 23011099 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | advanced cancer with brain metastasis |
| Cancer Subtype: | brain metastases from human epidermal growth factor receptor 2-positive breast cancerhuman epidermal growth factor receptor 2positive breast cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase II study |
| Key Patients Feature: | human epidermal growth factor receptor 2overexpressing MBC patients, defined as immunohistochemistry (IHC) 3 or IHC 2 and fluorescence insitu hybridization (FISH) positive, in which the cutoffsignal ratio of human epidermal growth factor receptor 2 gene copies to chromosome 17applied was 2.0, who developed brain metastases andmet all the following criteria, were enrolled: (1) histologically confirmed stage IV invasive breast cancer, (2)Eastern Cooperative Oncology Group Performance Status(ECOG PS) 0-2, (3) at least one measurable lesion in thebrain, defined as lesion C10 mm in longest dimension, (4)prior treatment for brain metastases with WBRT and/orSRS, (5) prior treatment with trastuzumab, either alone orin combination with chemotherapy, (6) left ventricularejection fraction within the institutional range of normal asmeasured by echocardiogram, (7) normal organ and marrow functions defined as follows: absolute neutrophil countC1.0 9 109/l, hemoglobin C9 g/dl (after blood transfusion, if required), platelet count C50 9 109/l, albuminC2.5 g/dl, serum bilirubin B1.5 9 upper limit of normalrange (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) B5 9 ULN (with livermetastases) or B3 9 ULN (without liver metastases), andserum creatinine B2.0 mg/dl or calculated creatinineclearance C25 ml/min by the Cockcroft and Gault method. |
| Biomarker: | human epidermal growth factor receptor 2overexpressing |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Lapatinib was administered at a starting dose of 750 mg, twice daily (total daily dose, 1, 500 mg). |
| Primary End Point: | efficacy, safety, and pharmacokinetics |
| Secondary End Point: | NA |
| Patients Number: | 6 |
| Trial Results | |
| DLT_MTD: | lapatinib monotherapy 750 mg given twice daily |
| Objective Response Rate: | NA |
| 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 most frequent toxicities were diarrhea and rash. Most of the events were grade 1 or 2, and the only grade 3 events were decreased lymphocyte count and increased ALT, noted in one patient each. Adverse events requiring dose reduction in lapatinib were reported in two patients: one patient with increased ALT and the second with increased blood bilirubin. |
| Conclusions: | These results suggest that lapatinib monotherapy 750 mg given twice daily can exert some efficacy and has potential as a clinically meaningful treatment option for Japanese human epidermal growth factor receptor 2overexpressing breast cancer patients with brain metastases after cranial radiation. |