Entry Detail
| General information | |
| Database: | DB01062 |
| Objective: | Lapatinib Versus Placebo Added to Paclitaxel in the Treatment ofHuman Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancer |
| Authors: | Zhongzhen Guan |
| Title: | Randomized trial of lapatinib versus placebo added to paclitaxel in the treatment of human epidermal growth factor receptor 2overexpressing metastatic breast cancer. |
| Journal: | journal of clinical oncology |
| Year: | 2013 |
| PMID: | 23509322 |
| Trial Design | |
| Clinical Trial Id: | NCT00281658 |
| 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: | paclitaxel+lapatinib |
| Study Type: | a randomized, doubleblind, placebocontrolled, multicenterphase III study |
| Key Patients Feature: | Patients with histologically confirmed invasive stage IV breast cancer overexpressing human epidermal growth factor receptor 2 (centrally determined by fluorescent in situ hybridization) were eligible. Noprior treatment for metastatic disease was allowed, with the exception ofhormonal treatment for patients with hormone receptor- positive disease. Prior trastuzumab and/or taxane as neoadjuvant or adjuvant therapy were permitted provided therapy was completed more than and equal to 12 months before study entry. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.0, adequate organ function, and a left ventricular ejection fraction (LVEF) within the institutional range of normal. |
| Biomarker: | human epidermal growth factor receptor 2overexpressing |
| Biomark Analysis: | This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with human epidermal growth factor receptor 2positive MBC. |
| Control Group Info: | Placebo plus Paclitaxel |
| Treatment Info: | paclitaxel (80 mg/m2 intravenously once per week for 3 weeks every 4 weeks) and lapatinib (1, 500mgonceperday) or to paclitaxel (80 mg/m2 intravenously once per week for 3 weeks every 4 weeks) and placebo (once per day) byusing a 1:1 allocation and were stratified by metastatic disease sites (visceral or nonvisceral site only) and hormone receptor status (estrogen receptor-positive and/or progesterone receptor- positiveorestrogenreceptor-negativeandprogesteronereceptor-negative). |
| Primary End Point: | OS. |
| Secondary End Point: | progression free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety. |
| Patients Number: | 444 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified logrank P< .001). |
| Median OS A vs. C: | median OS was 27.8 versus 20.5 months, respectively. (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124) |
| Adverse Event(agent arm): | The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. |
| Conclusions: | This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with human epidermal growth factor receptor 2positive MBC. |