Entry Detail
| General information | |
| Database: | DB01053 |
| Objective: | Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer |
| Authors: | Xavier Pivot |
| Title: | CEREBEL (EGF111438): a phase III, Randomized, OpenLabel Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Human Epidermal Growth Factor Receptor 2Positive Metastatic Breast Cancer. |
| Journal: | journal of clinical oncology |
| Year: | 2015 |
| PMID: | 25605838 |
| Trial Design | |
| Clinical Trial Id: | NCT00820222 |
| 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 Plus Capecitabine Versus Trastuzumab Plus Capecitabine |
| Study Type: | a phase III, randomized, multicenter, openlabel study in women with human epidermal growth factor receptor IIpositive MBC. patients were randomly assigned (I:I) to receive lapatinibcapecitabine or trastuzumabcapecitabine and stratified according to prior trastuzumab and prior metastatic therapy. |
| Key Patients Feature: | women more than and equal to 18 years old with histologically confirmedhuman epidermal growth factor receptor 2positiveMBC(human epidermal growth factor receptor 2score>2.2 by fluorescence in situ hybridization and/or 3+ amplification by immunohistochemistry or chromogenic/ silver in situ hybridization). No centralized review of human epidermal growth factor receptor 2 status was undertaken, and testing was performed as per the institution¡¯s local laboratory methods. patients were required to have received prior anthracycline and/or taxanes for (neo)adjuvant or metastatic disease. Prior trastuzumab was allowed but not required. Eastern Cooperative Oncology Group performance status less than and equal to 2 and adequate organ function were required. All patients signed an informed consent form. No history of CNS metastases or presence of CNS metastases at baseline was permitted; baseline brain MRI scans were an eligibilityscreening requirement to exclude potential participants withasymptomatic metastases. |
| Biomarker: | Human Epidermal Growth Factor Receptor 2Positive |
| Biomark Analysis: | NA |
| Control Group Info: | Trastuzumab Plus Capecitabine |
| Treatment Info: | lapatinibcapecitabine (lapatinib 1, 250 mg per day; capecitabine 2, 000 mg/m2 per day on days 1 to 14 every per day on days 1 to 21 days) or trastuzumabcapecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2, 500 mg/m2 14 every 21 days). |
| Primary End Point: | incidence of CNS metastases as first site of relapse. Secondary end points included progression free survival (PFS) and overall survival (OS). |
| Secondary End Point: | NA |
| Patients Number: | 540 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | ORRs were similar in both treatment arms in the ITT population (27% [73 of 271 patients] for lapatinibcapecitabine v32%[85 of269 patients] for trastuzumabcapecitabine; P=.2731) |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | MedianPFSwas shorter for lapatinibcapecitabine compared with trastuzumabcapecitabine (6.6 months]95% CI, 5.7 to 8.1 months[ v 8.1 months[95% CI, 6.1 to 8.9 months], respectively; HR, 1.30; 95% CI, 1.04 to 1.64) |
| Median OS A vs. C: | Median OS time was 22.7 months (95% CI, 19.5 months to not reached) for lapatinibcapecitabine compared with 27.3 months (95% CI 23.7 months to not reached) for trastuzumabcapecitabine (HR, 1.34;95% CI, 0.95 to 1.90) |
| Adverse Event(agent arm): | The most common adverse events (AEs) were consistent between treatment arms with the exception of diarrhea, nausea, rash, and hyperbilirubinemia, which had a higher incidence with lapatinibcapecitabine than with trastuzumabcapecitabine. AEs leading to study treatment discontinuation were reported for 11% of patients (29 of 269 patients) in the lapatinibcapecitabine arm and 13% ofpatients (35 of267 patients) in the trastuzumabcapecitabine arm. Serious AEs (SAEs) were reported for 13% ofpatients (34 of269 patients) in the lapatinibcapecitabine arm and17% ofpatients (45 of 267 patients) in the trastuzumabcapecitabine arm. SAEs leading to study medication withdrawal were reported in 3% ofpatients (seven of 269 patients) in the lapatinibcapecitabine arm and 4% ofpatients (12 of 267 patients) in the trastuzumabcapecitabine arm. The majority of SAEs were reported by less than 2% of patients in either arm, except for diarrhea, pyrexia, neutropenia, and pulmonary embolism. The rate ofgrade 3 or 4 neutropenia was less than7%in both arms; no cases ofneutropenic fever occurred. Few cases ofserious cardiac dysfunction were reported (none in the lapatinibcapecitabine arm and <1% in the trastuzumabcapecitabine arm). |
| Conclusions: | CEREBEL is inconclusive for the primary end point, and no difference was detected bettheyen lapatinbcapecitabine and trastuzumabcapecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumabcapecitabine in the overall population. Hotheyver, lapatinibcapecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen andor when treatment was given as first or secondline therapy in the metastatic setting. |