Entry Detail
| General information | |
| Database: | DB01057 |
| Objective: | Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer. |
| Authors: | M Toi |
| Title: | Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patientsphase II studies. |
| Journal: | British Journal of Cancer |
| Year: | 2009 |
| PMID: | 19844234 |
| Trial Design | |
| Clinical Trial Id: | NCT00320411 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multicentre, singlearm, openlabel studies involving IIIII centres in Japan. |
| Key Patients Feature: | female aged 20-74 years with confirmed advanced (stage IIIb or IIIc with T4 lesion) or MBC that had progressed on prior anthracycline and taxanecontaining regimens. All patients with human epidermal growth factor receptor 2 overexpression had received more than and equal to 6 weeks of prior trastuzumab. Eligible patients had measurable lesions as defined by RECIST; an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; left ventricular ejection fraction (LVEF) within the institutional normal range (or more than and equal to 50%); adequate renal, hepatic and haematologic functions. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | NA |
| Treatment Info: | oral lapatinib given 1500 mg once daily in patients with advanced or MBC. All patients progressed on anthracyclines and taxanes; human epidermal growth factor receptor 2positive patients had also progressed on trastuzumab. |
| Primary End Point: | objective response rate (ORR: confirmed complete response (CR) and partial response (PR)) according to response evaluation criteria in solid tumours (RECIST) and determined by an independent review committee. |
| Secondary End Point: | clinical benefit rate (CBR: CR, PR and stable disease (SD) for X24 weeks); timetoprogression (TTP); and overall survival (OS). |
| Patients Number: | 122 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 19.0% (95% CI: 11.8-28.1) |
| Disease Control Rate: | PD: 41% (41 out of 100) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | The median OS was 58.3 weeks (25th, 75th percentiles: 26.2, 64.8) in human epidermal growth factor receptor 2positive patients and 40.0 weeks (25th, 75th percentiles: 18.3, 69.3) in human epidermal growth factor receptor 2negative patients. |
| Adverse Event(agent arm): | There were 27 nonfatal serious AEs in 19 patients, 13 were possibly related to lapatinib. The only lapatinibrelated serious AEs occurred in more than one patient were anorexia (n=3, 2.5%) and left ventricular dysfunction (n= 2, 1.6%). Both patients experiencing left ventricular dysfunction remained on lapatinib and the event later resolved. Three patients died because of disease progression. One patient experienced fatal AEs (increase in ¦Ãglutamyl transferase and bilirubin); the events, deemed unrelated to lapatinib, were due to liver metastases progression. The other two experienced 'unexpectedly rapid¡¯ disease progression; one in a human epidermal growth factor receptor 2negative patient. |
| Conclusions: | Lapatinib monotherapy had shown antitumour activity in Japanese patients with human epidermal growth factor receptor 2positive MBC that relapsed after trastuzumabbased therapy, including those with brain metastases. Patients benefiting from lapatinib may have biomarker profiles differing from that reported for trastuzumab. |