CMTTdb

An integrated database for cancer molecular targeted thearpies

Entry Detail


General information
Database:DB01055
Objective:Lapatinib Plus Trastuzumab Plus Paclitaxel in FirstLine human epidermal growth factor receptor 2Positive Metastatic Breast Cancer
Authors:FRANCISCO J. ESTEVA
Title:An openlabel safety study of lapatinib plus trastuzumab plus paclitaxel in firstline human epidermal growth factor receptor 2positive metastatic breast cancer.
Journal:The Oncologist
Year:2013
PMID:23697602
Trial Design
Clinical Trial Id:NCT00272987
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:13
Therapeutic Combination Content:lapatinib plus trastuzumab plus paclitaxel
Study Type:EGFI04III8III was initially designed as a randomized, doubleblind, placebocontrolledphase III study comparing the efficacy and tolerability of paclitaxel plus trastuzumab plus lapatinib with paclitaxel plus trastuzumab plus placebo in women with human epidermal growth factor receptor IIamplified MBC. Prior to the start of the planned randomizedphase of this trial, an openlabel safety study was conducted. The results of this safety study are presentedhere.the phaseIIIrandomizedphaseofthisstudydidnot occur because of the high rates of grade III diarrhea at standard doses of lapatinib (I, 000 mg) in this triple combination and the subsequenttimetakento recruit patients intothethreecohorts.
Key Patients Feature:womenagedmore than and equal to 18 years with histologically confirmed invasive stage IV breast cancer. All had tumors overexpressinghuman epidermal growth factor receptor 2(defined as3+ by immunohistochemistry[IHC] or HER2/neu gene amplification by fluorescence in situ hybridization [FISH] or 0 to 2+ by IHC and HER2/neu gene amplification by FISH). All women had a lesion measurable by Response Evaluation Criteria in Solid Tumors (RECIST) or assessable disease. Adequate organ function, a left ventricular ejection fraction (LVEF) within institutional normal range, and Eastern Cooperative Oncology Group (ECOG) performance statusof0or1werealsorequiredforenrollment.Previousadjuvant treatment with trastuzumab was permitted if 12 months had elapsed since its discontinuation; previous neoadjuvant/adjuvant treatment with taxanes was permitted if progression had occurred12ormoremonths after its completion.
Biomarker:human epidermal growth factor receptor 2positive
Biomark Analysis:NA
Control Group Info:NA
Treatment Info:Patients in cohort 1 received lapatinib (1000 mg/day) plus paclitaxel (80 mg/m2 per week, 3 of every 4 weeks); cohort 2 received lapatinib (1000 mg/day) plus paclitaxel (70 mg/m2 per week, 3 of every 4 weeks); and cohort 3 received lapatinib (750 mg/day) plus paclitaxel (80mg/m2 per week, 3 of every 4 weeks). All received standard trastuzumab dosing.
Primary End Point:assessment of doselimiting toxicities, safety, and tolerability of this combination.
Secondary End Point:NA
Patients Number:63
Trial Results
DLT_MTD:NA
Objective Response Rate:75% (47 out of 63 patients; 95% CI: 62.1-84.7) . Response rates were 79%(23outof29patients;95%CI: 60.3-92.0) in cohort 1;71%(10outof14patients; 95% CI: 41.9-91.6) in cohort 2; and 70% (14 out of 20 patients; 95% CI: 45.7-88.1) in cohort 3.
Disease Control Rate:NA
Median Time to Progression:NA
Median PFS A vs. C:NA
Median OS A vs. C:NA
Adverse Event(agent arm):The most frequent adverse events (AEs) for all cohorts werediarrhea (89%), rash (79%), fatigue (73%), alopecia (63%), nausea (63%), and vomiting (40%). In cohorts 1 and 2, the incidence of grade 3 diarrhea was 62% and 50%, respectively; in cohort 3, the incidence was 25% (with prophylactic loperamide). Dehydration was the most frequent serious AE (10%). Across cohorts, overall response rate was 75%.
Conclusions:The doselimiting toxicity of paclitaxel, trastuzumab, and lapatinib in firstline human epidermal growth factor receptor 2positive MBC was diarrhea. Of the triplet combinations tested, the cohort receiving 750mgday dose of lapatinib had the lotheyst incidence of diarrhea; therefore, this dose should be used in further studies on the treatment of MBC.