Randomised Phase 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 virus-negative disease.

Abstract

BACKGROUND:

This randomised Phase 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.

PATIENTS AND METHODS:

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 was complete response rate (CRR) by independent review 6 months post-CRT.

RESULTS:

Sixty-seven patients (median age 56 years; 97% Eastern Cooperative Oncology Group performance status ≤1; 82% stage IV) were recruited. CRT dose intensities were unaffected by lapatinib: median radiation dose 70 Gy (lapatinib, placebo), duration 49 (lapatinib) and 50 days (placebo); median cisplatin dose 260 mg/m(2) (lapatinib) and 280 mg/m(2) (placebo). Lapatinib combined with CRT was well-tolerated. 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. CRR at 6 months post-CRT was 53% with lapatinib versus 36% with placebo in the intent-to-treat population. The progression-free survival (PFS) and overall survival rates at 18 months were 55% versus 41% and 68% versus 57% for the lapatinib and placebo arms, respectively. The difference between study arms was greatest in p16-negative disease (median PFS >20.4 months [lapatinib] versus 10.9 [placebo]).

CONCLUSION:

Lapatinib combined with CRT is well-tolerated with numeric increases in CRR at 6 months post-CRT and median PFS in p16-negative disease.

• Authors: Kevin Harrington, Alain Berrier, Martin Robinson, Eva Remenar, Martin Housset, Fernando Hurtado de Mendoza, Jérôme Fayette, Hisham Mehanna, Iman El-Hariry, Natalie Compton, Natalie Franklin, Nigel Biswas-Baldwin, Mike Lau, Philippe Legenne, Rejnish Kumar
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 49 Issue 7 Pg. 1609-18 (May 2013) ISSN: 1879-0852 [Electronic] England
• PMID: 23265705 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Cyclin-Dependent Kinase Inhibitor p16
• Quinazolines
• Lapatinib
• EGFR protein, human
• ErbB Receptors
• Cisplatin

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Squamous Cell (metabolism, pathology, therapy)
• Chemoradiotherapy (adverse effects, methods)
• Cisplatin (administration & dosage, adverse effects)
• Cyclin-Dependent Kinase Inhibitor p16 (analysis)
• Diarrhea (etiology)
• Disease-Free Survival
• Double-Blind Method
• Drug Administration Schedule
• ErbB Receptors (analysis)
• Exanthema (etiology)
• Female
• Head and Neck Neoplasms (metabolism, pathology, therapy)
• Humans
• Immunohistochemistry
• Lapatinib
• Male
• Middle Aged
• Neoplasm Staging
• Papillomaviridae (physiology)
• Quinazolines (administration & dosage, adverse effects, therapeutic use)
• Radiotherapy Dosage
• Treatment Outcome