Entry Detail
| General information | |
| Database: | DB00652 |
| Objective: | Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Their study assessed the combination of both drugs as treatment for patients with human epidermal growth factor receptor 2positive BC and BM. |
| Authors: | de Azambuja E, et al |
| Title: | Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with human epidermal growth factor receptor 2positive metastatic breast cancer: the LAPTEM trial. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 24013582 |
| Trial Design | |
| Clinical Trial Id: | NCT00614978 |
| 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: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | temozolomide plus lapatinib |
| Study Type: | an openlabelphase I study |
| Key Patients Feature: | NA |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Temozolomide was given orally, once a day, at three dose levels: 100, 150and 200 mg/m2/day, days 1-5. Lapatinib was given orally, once a day at threedose levels: 1000, 1250, 1500 mg/day. Both agents were given until progression of the disease, intolerable toxicity or a maximum of six cycles, whichever came first. A cycle was defined as 28 days of therapy. |
| Primary End Point: | doselimiting toxicities (DLTs) and maximumtolerated dose (MTD) |
| Secondary End Point: | objective response rate, clinical benefit and duration of response |
| Patients Number: | 18 |
| Trial Results | |
| DLT_MTD: | The lapatinibtemozolomide regimen showed a favorable toxicity profile because the MTD could not be reached |
| Objective Response Rate: | NA |
| Disease Control Rate: | 0.67 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2.60 months [95% confidence interval (CI): 1.82-3.37] |
| Median OS A vs. C: | 10.94 months (95% CI: 1.09-20.79) |
| Adverse Event(agent arm): | The most common adverse events (AEs) were fatigue, diarrhea and constipation. |
| Conclusions: | The lapatinibtemozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions. |