Entry Detail
| General information | |
| Database: | DB00555 |
| Objective: | The treatment of recurrent transitional cell carcinoma (TCC) remains an unmet clinical need. This study assessed lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER2, as secondline therapy in patients with locally advanced or metastatic TCC. |
| Authors: | W¨¹lfing C, et al |
| Title: | A singlearm, multicenter, openlabelphase 2 study of lapatinib as the secondline treatment of patients with locally advanced or metastatic transitional cell carcinoma. |
| Journal: | cancer |
| Year: | 2009 |
| PMID: | 19399906 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | advanced transitional cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a singlearm, multicenter, openlabel, prospectivephase II study |
| Key Patients Feature: | Eligible patients were aged 18 years, andhad histologically confirmed measurable locally advancedor metastatic TCC with documented disease progression after firstline platinumbased therapy. Patients were requiredto have Karnofsky performance status of 70, a left ventricular ejection fraction (LVEF) within institutional normallimits assessed by a multigated acquisition scan or echocardiography, and adequate organ function (granulocyte count>1500/mm3, platelet count >100, 000/mm3, hemoglobin>9 g/dL, serum creatinine 1.5 mg/dL, total bilirubin<1.5 times upper limit of normal [ULN], and alanine aminotransferase <3 times ULN). Prior systemic neoadjuvantand/or adjuvant therapies were permitted. Confirmed 1t, 2t, or 3t expression of EGFR and/or HER2 by immunohistochemistry (IHC) was required before enrollment. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received oral lapatinib at a dose of 1250 mg once daily. Treatment was continued until disease progression, withdrawal from the study because of unacceptable toxicity, or withdrawal of consent. |
| Primary End Point: | objective tumor response rate |
| Secondary End Point: | safety, time to disease progression, and overall survival. |
| Patients Number: | 59 |
| Trial Results | |
| DLT_MTD: | The most common grade 3 and/or 4 AEswere vomiting (7%), diarrhea (3%), dehydration (3%), and hyponatremia (3%). |
| Objective Response Rate: | The primaryendpoint of an objective response rate (ORR) >10% was observed in 1.7% (95% confidence interval [95%CI], 0.0%9.1%) of patients; however, 18 (31%; 95% CI, 19%44%) patients achieved stable disease (SD). Themedian time to disease progression and overall survival (OS) were 8.6 weeks (95% CI, 8.0 weeks11.3weeks) and 17.9 weeks (95% CI, 13.1 weeks30.3 weeks), respectively. Clinical benefit (ORR and SD) wasfound to be correlated with EGFR overexpression (P .029), and, to some extent, HER2 overexpression. |
| Disease Control Rate: | NA |
| Median Time to Progression: | 8.6 weeks (95% CI, 8.0 weeks11.3 weeks) |
| Median PFS A vs. C: | The median PFS were 4.5 months, in Group A and 3.3 months and 7.4 months, respectively, in Group B |
| Median OS A vs. C: | 17.9 weeks (95% CI, 13.1 weeks30.3 weeks) |
| Adverse Event(agent arm): | The most common grade 3 and/or 4 Aes were vomiting (7%), diarrhea (3%), dehydration (3%), and hyponatremia (3%). |
| Conclusions: | The study was considered to be negative because it did not meet its primary endpoint; hotheyver, further analysis demonstrated an improvement in OS in a subset of patients with tumors overexpressing EGFR andor HER2, which is encouraging and warrants further investigation. |