Entry Detail
| General information | |
| Database: | DB01047 |
| Objective: | Chemotherapy and Lapatinib or Trastuzumab in Treating Women With human epidermal growth factor receptor 2/NeuPositive Metastatic Breast Cancer |
| Authors: | Karen A. Gelmon |
| Title: | Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31. |
| Journal: | journal of clinical oncology |
| Year: | 2015 |
| PMID: | 25779558 |
| Trial Design | |
| Clinical Trial Id: | NCT00667251 |
| 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: | Lapatinib or Trastuzumab Plus Taxane Therapy |
| Study Type: | a randomized openlabel internationalphase III trial. |
| Key Patients Feature: | human epidermal growth factor receptor 2positive metastatic BC, Eastern Cooperative Oncology Group performance status 0 to 2, no prior therapywith cytotoxics or biologics for recurrent or advanced disease, baseline left ventricular ejection fraction (LVEF) more than and equal to 50% (determined by echocardiography or multiplegated acquisition scanning), measurable or nonmeasurable disease defined by RECIST (version 1.0) criteria, and no major endorgan disease. Prior (neo)adjuvant treatment with antihuman epidermal growth factor receptor 2 agent and/or taxane was allowed provided the last dose was more than and equal to 12 months before random assignment. Prior endocrine therapy or radiotherapy was permitted provided more than and equal to 2 weeks had elapsed from cessation. |
| Biomarker: | Human Epidermal Growth Factor Receptor 2Positive |
| Biomark Analysis: | in patients with centrally confirmed human epidermal growth factor receptor 2positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03). |
| Control Group Info: | Trastuzumab + taxane 24 weeks ยกรบ Trastuzumab until PD |
| Treatment Info: | Taxane choice was discretionary: intravenous paclitaxel 80 mg/m2 once per week on days 1, 8, and 15 of a 28day schedule or docetaxel 75 mg/m2 once every 3 weeks. The lapatinib dose was 1, 250 mg, administered daily orally when combined with taxane for 24 weeks; it was then increased to 1, 500 mg daily as monotherapy. Intravenous trastuzumab was administered once per week for 24 weeks with onceperweek paclitaxel (4 mg/kg bolus followed by 2 mg/kg maintenance) or on a onceevery3week basis (8 mg/kg bolus followed by 6 mg/kg maintenance) when combined with docetaxel once every 3 weeks. During monotherapy, patients received trastuzumab 6 mg/kg once every 3 weeks. |
| Primary End Point: | intentiontotreat (ITT) progression free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed human epidermal growth factor receptor 2positive tumors. |
| Secondary End Point: | NA |
| Patients Number: | 652 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 139 (54%) in the lapatinib group and 148 (55%) in the trastuzumab group. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 9.0 months with lapatinib and 11.3 months with trastuzumab (stratified HR, 1.37; 95% CI, 1.13 to 1.65;P=.001) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Incidences of rash and diarrhea were higher in the lapatinib arm, but most were grade 1 or 2. During combination therapy, grade 3 or 4 rash occurred in 8% of patients receiving lapatinib compared with0%ofthose receiving trastuzumab (P < .001), and grade 3 or 4 diarrhea was reported in 19% of those receiving lapatinib compared with1%ofthose receiving trastuzumab (P < .001). With 188 patients enrolled, higher febrile neutropenia rates were seen with lapatinib plus docetaxel (17.3%) compared with trastuzumab plus docetaxel (2.0%). |
| Conclusions: | As firstline therapy for human epidermal growth factor receptor 2positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane. |