Entry Detail
| General information | |
| Database: | DB00383 |
| Objective: | Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human EGFR2 (HER2) tyrosine kinases. This study investigated the pharmacodynamic and clinical effects of lapatinib in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). |
| Authors: | Del Campo JM, et al |
| Title: | Effects of lapatinib monotherapy: results of a randomisedphase II study in therapynaive patients with locally advanced squamous cell carcinoma of the head and neck. |
| Journal: | Br J Cancer. |
| Year: | 2011 |
| PMID: | 21829197 |
| Trial Design | |
| Clinical Trial Id: | NCT00371566 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multinational, randomised, singleblinded, placebocontrolled study, |
| Key Patients Feature: | Adults of at least 18 years of age with newly diagnosed stageIII/IVA/IVB SCCHN undergoing chemoradiation therapy (CRT)were eligible. Other criteria included Eastern Cooperative Oncology Group performance status of 0, 1, or 2; adequate renal, hepatic, and bone marrow function; and normal left ventricular ejectionfraction assessed by echocardiogram or multigated acquisitionscan |
| Biomarker: | Biological evaluations |
| Biomark Analysis: | There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation. |
| Control Group Info: | A:lapatinib B:placebo |
| Treatment Info: | therapynaive patients with locally advanced SCCHN were randomised (2 : 1) to receive lapatinib or placebo for 26 weeks before chemoradiation therapy (CRT). |
| Primary End Point: | apoptotic index (AI); |
| Secondary End Point: | proliferation rategiven by proliferation index (PI) (percent proliferating cells/totalnumber of cells), ORR, adverse events, and correlative biomarkeranalyses. |
| Patients Number: | 107 |
| Trial Results | |
| DLT_MTD: | Mucosalinflammation, asthenia, odynophagia, and dysphagia were the most commonly reported adverse events with lapatinib. |
| Objective Response Rate: | In a subset of 40 patients that received X4 weeks of lapatinib or placebo, objective response rate (ORR) was 17% (n 4/24) vs 0% (n 0/16). In the lapatinib singleagent responders, all had EGFRoverexpression, 50% had EGFR amplification, and 50% had human epidermal growth factor receptor 2 expression by immunohistochemistry (including one patient withhuman epidermal growth factor receptor 2 amplification) |
| 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): | There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation. Mucosal inflammation, asthenia, odynophagia, and dysphagia were the most commonly reported adverse events with lapatinib. |
| Conclusions: | Shortterm lapatinib monotherapy did not demonstrate apoptotic changes, but provided evidence of clinical activity in locally advanced SCCHN, and warrants further investigation in this disease. |