Entry Detail
| General information | |
| Database: | DB00381 |
| Objective: | This randomisedphase II study assessed the activity and safety of concurrent chemoradiotherapy (CRT) and lapatinib followed by maintenance treatment in locally advanced, unresected stage III/IVA/IVB head and neck cancer. |
| Authors: | Harrington K, et al |
| Title: | Randomisedphase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: rationale for future randomised trials in human papilloma virusnegative disease. |
| Journal: | Eur J Cancer. |
| Year: | 2013 |
| PMID: | 23265705 |
| Trial Design | |
| Clinical Trial Id: | NCT00387127 |
| Agent: | lapatinib |
| Target: | Epidermal growth factor receptor Receptor proteintyrosine kinase erbB2 |
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | oral lapatinib combined with chemoradiotherapy |
| Study Type: | Randomisedphase II doubleblindstudy |
| Key Patients Feature: | Eligible patients had histologicallyconfirmed, unresected stage III/IVA/IVB HNSCC of at least 1 of thefollowing sites: oral cavity, oropharynx, hypopharynxand larynx. Other inclusion criteria included: EuropeanCooperative Oncology Group Performance Status 0, 1or 2; adequate renal, hepatic and haematological function; and normal left ventricular ejection fraction.Patients with T1N1, T2N1 or metastatic disease and patients who had received any prior or current treatment for invasive HNSCC were excluded. Initially, onlypatients with EGFR overexpression (3+ by immunohistochemistry [IHC]) were included. |
| Biomarker: | p16 status |
| Biomark Analysis: | The difference betweenstudy arms was greatest in p16negative disease (median PFS >20.4 months [lapatinib] versus10.9 [placebo]). |
| Control Group Info: | A:CRT and placebo followed by placebo B: concurrent CRT and lapatinib followed by lapatinib |
| Treatment Info: | patients were randomised 1:1 to concurrent CRT and placebo followed by placebo or concurrent CRT and lapatinib followed by lapatinib. Treatment continued until disease progression or study withdrawal. |
| Primary End Point: | complete response rate (CRR) by independent review 6 months postCRT. |
| Secondary End Point: | progression free survival (PFS), overall survival (OS), locoregional control, distant relapse, biomarkers and safety. |
| Patients Number: | 67 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | complete response rate (CRR) at 6 months postCRT was 53% with lapatinib versus 36% with placebo in the intenttotreat population |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The progression free survival (PFS) rates at 18 months were 55% versus 41% for the lapatinib and placebo arms, respectively. |
| Median OS A vs. C: | overall survival rates at 18 months were 68% versus 57% for the lapatinib and placebo arms, respectively. |
| Adverse Event(agent arm): | Lapatinib combined with CRT was welltolerated. Grade 3/4 toxicities during CRT were balanced between arms, with the exception of an excess of grade 3 diarrhoea (6% versus 0%) and rash (9% versus 3%) and two grade 4 cardiac events in the lapatinib arm. |
| Conclusions: | Lapatinib combined with CRT is welltolerated with numeric increases in CRR at 6 months postCRT and median PFS in p16negative disease. |