Entry Detail
| General information | |
| Database: | DB01060 |
| Objective: | Lapatinib in a Randomized Trial of Paclitaxel With Lapatinib or Placebo As FirstLine Treatment in human epidermal growth factor receptor 2Negative or Unknown Metastatic Breast Cancer |
| Authors: | Richard S. Finn |
| Title: | Estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (human epidermal growth factor receptor 2), and epidermal growth factor receptor expression and benefit from lapatinib in a randomized trial of paclitaxel with lapatinib or placebo as firstline treatment in human epidermal growth factor receptor 2negative or unknown metastatic breast cancer. |
| Journal: | journal of clinical oncology |
| Year: | 2009 |
| PMID: | 19620495 |
| Trial Design | |
| Clinical Trial Id: | NCT00075270 |
| 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: | paclitaxel with lapatinib |
| Study Type: | a phase III trial of lapatinib and paclitaxel versus paclitaxel and placebo, demonstrated lapatinib does not significantly benefit human epidermal growth factor receptor IInegative or human epidermal growth factor receptor IIunselected patients with MBC. |
| Key Patients Feature: | women with advanced breast cancer (stage III or IV) previously untreated in the metastatic setting |
| Biomarker: | human epidermal growth factor receptor 2negative or human epidermal growth factor receptor 2unselected |
| Biomark Analysis: | Although subgroups are small, these analyses support the hypothesis that semiquantitative determination of hormone receptor status may be a surrogate for EGFR and/or human epidermal growth factor receptor 2 dependency. EGFR expression was not correlated with benefit from lapatinib. |
| Control Group Info: | paclitaxel plus placebo |
| Treatment Info: | paclitaxel 175 mg/m2 intravenously every 3 weeks with either oral lapatinib 1, 500 mg daily or placebo. |
| Primary End Point: | time to progression (TTP). |
| Secondary End Point: | NA |
| Patients Number: | 579 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Lapatinib improved median EFS in human epidermal growth factor receptor 2amplified, ER or PRpositive MBC (n = 36; 5.7 v 4.5 months; P= .351); benefit was greater and statistically significant in human epidermal growth factor receptor 2amplified, ERnegative, PRnegative MBC (n = 42; 8.3 v 5.0 months; P= .007). In human epidermal growth factor receptor 2negative, ERpositive MBC, median EFS improvement varied by degree of PR expression (Hscore): no benefit if PRstrong (n = 133; 9.3 v 7.3 months; P= .373), benefit if PRtheyak (n = 50; 7.3 v 2.4 months; P= .026), and potential antagonism if PRnegative (n = 40; 3.7 v7.2 months; P= .004). No benefit was seen in triplenegative MBC (n = 131; median EFS, 4.6 v 4.8 months; P= .255). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | Although subgroups are small, these analyses support the hypothesis that semiquantitative determination of hormone receptor status may be a surrogate for EGFR andor human epidermal growth factor receptor 2 dependency. |