Entry Detail
| General information | |
| Database: | DB01059 |
| Objective: | the addition of pazopanib to lapatinib as firstline therapy in patients with human epidermal growth factor receptor 2positive advanced breast cancer |
| Authors: | Stephen R. D. Johnston |
| Title: | A randomized and openlabel trial evaluating the addition of pazopanib to lapatinib as firstline therapy in patients with human epidermal growth factor receptor 2positive advanced breast cancer. |
| Journal: | Breast Cancer Res Treat. |
| Year: | 2013 |
| PMID: | 23283526 |
| Trial Design | |
| Clinical Trial Id: | NCT00347919 |
| 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: | 1 |
| Therapeutic Combination Content: | pazopanib plus lapatinib |
| Study Type: | This study (VEGII0007) was initially designed as a randomized, multicenter, phase II study (NCT00III479I9). |
| Key Patients Feature: | women were more than and equal to 18 years of age with histologically confirmed invasive breast cancer. Patients must have had inoperable stages IIIb, IIIc with T4 lesion, or stage IV disease at primary diagnosis or at relapse after curativeintent surgery. For patients in Cohort 1, tumors were required to have human epidermal growth factor receptor 2 gene amplification as measured by fluorescence in situ hybridization (FISH). The eligibility criteria for the Cohort 2 were amended to also include women whose human epidermal growth factor receptor 2 overexpression was documented based on a prior immunochemistry value of 3+. Recruitment to Cohort 1 occurred primarily at Asian and South American centers; recruitment to Cohort 2 occurred primarily at US and European sites. Prior anticancer therapy (except hormonal therapy) for metastatic or recurrent disease was not permitted. Eligible patients had measurable disease according to Response Evaluation Criteria in Solid Tumors (RECISTs) version 1.0; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; adequate hematologic, renal, and hepatic function; and cardiac ejection fraction within the institutional normal range. |
| Biomarker: | human epidermal growth factor receptor 2positive |
| Biomark Analysis: | NA |
| Control Group Info: | Cohort 1, patients were randomly assigned to lapatinib 1, 000 mg plus pazopanib 400 mg or lapatinib 1, 500 mg monotherapy; Cohort 2, patients received lapatinib 1, 500 mg plus pazopanib 800 mg. |
| Treatment Info: | Cohort 1, patients were randomly assigned to lapatinib 1, 000 mg plus pazopanib 400 mg or lapatinib 1, 500 mg monotherapy; Cohort 2, patients received lapatinib 1, 500 mg plus pazopanib 800 mg. |
| Primary End Point: | week12 progressive disease rate (PDR) for Cohort 1. |
| Secondary End Point: | week12 response rate (RR) for Cohort 2. Efficacy was assessed in patients with centrally confirmed human epidermal growth factor receptor 2 positivity (modified intenttotreat population [MITT]). |
| Patients Number: | 190 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | There was no difference in PFS (HR = 1.30; P = 0.314) or overall survival (HR = 0.91; P = 0.7488) between the two treatment arms in Cohort 1. In Cohort 2, week12 RR was 33.3 % (90 % CI: 20.5, 48.3). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | In Cohort 1, grade 3/4 adverse events (AEs) included diarrhea (combination, 9 %; lapatinib, 5 %) and hypertension (combination, 5 %; lapatinib, 0 %). Grades 3/4 AEs in Cohort 2 included diarrhea (40 %), hypertension (5 %), and fatigue (5 %). Alanine aminotransferase elevations[5 times the upper limit of normal occurred in Cohort 1 (combination, 18 %; lapatinib, 5 %) and Cohort 2 (20 %). |
| Conclusions: | the combination of lapatinib plus pazopanib did not improve PDR compared with lapatinib monotherapy, although RR was increased. Toxicity was higher with the combination, including increased diarrhea and liver enzyme elevations. |