Entry Detail
| General information | |
| Database: | DB00647 |
| Objective: | One third of women with advanced human epidermal growth factor receptor 2 (HER2)positive breast cancer develop brain metastases; a subset progress in the CNS despite standard approaches. Medical therapies for refractory brain metastases are neither wellstudied nor established. they evaluated the safety and efficacy of lapatinib, an oral inhibitor of epidermal growth factor receptor (EGFR) and HER2, in patients with HER2positive brain metastases. |
| Authors: | Lin NU, et al |
| Title: | Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2positive breast cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2008 |
| PMID: | 18421051 |
| 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 cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II Trial |
| Key Patients Feature: | at least 18 years of age.Eligible patients had at least one measurable lesion in the brain (definedas any lesion 1.0 cm in longest dimension), an Eastern Cooperative Oncology Group performance status 0 to 2, life expectancy 12 weeks, the ability toswallow oral medications, and the absence of a prior malignancy besides breastcancer unless treated with curative intent. Patients were required to have a leftventricular ejection fraction (LVEF) within institutional normal limits, absolute neutrophil count of at least 1, 000/ L, platelet count of at least 75, 000/ L, bilirubin no more than 1.5 upper limit of normal (ULN), AST and ALT nomore than 5 ULN, and creatinine clearance of at least 25 mL/min |
| Biomarker: | HER2positive |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received lapatinib 750 mg orally twice a day. Tumor response was assessed by magnetic resonance imaging every 8 weeks. |
| Primary End Point: | objective response (complete response [CR] plus partial response [PR]) in the CNS by RECIST |
| Secondary End Point: | objective response in nonCNS sites, time to progression, overall survival, and toxicity. |
| Patients Number: | 39 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Of 39 patients, one achieved a PR, for anoverall CNS response rate of 2.6% (95% conditional CI, 0.21% to 26%; Fig 1; Table 3) |
| Disease Control Rate: | 0.178 |
| Median Time to Progression: | 3.0 months (95% CI, 2.3 to 3.7 months). |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events (AEs) were diarrhea (grade 3, 21%) and fatigue (grade 3, 15%). |
| Conclusions: | The study did not meet the predefined criteria for antitumor activity in highly refractory patients with HER2positive brain metastases. Because of the volumetric changes observed in our exploratory analysis, further studies are underway utilizing volumetric changes as a primary end point. |