TY - JOUR
T1 - Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck
T2 - Rationale for future randomised trials in human papilloma virus-negative disease
AU - Harrington, Kevin
AU - Berrier, Alain
AU - Robinson, Martin
AU - Remenar, Eva
AU - Housset, Martin
AU - de Mendoza, Fernando Hurtado
AU - Fayette, Jérôme
AU - Mehanna, Hisham
AU - El-Hariry, Iman
AU - Compton, Natalie
AU - Franklin, Natalie
AU - Biswas-Baldwin, Nigel
AU - Lau, Mike
AU - Legenne, Philippe
AU - Kumar, Rejnish
N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.
PY - 2012
Y1 - 2012
N2 - 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 70Gy (lapatinib, placebo), duration 49 (lapatinib) and 50 days (placebo); median cisplatin dose 260mg/m(2) (lapatinib) and 280mg/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.
AB - 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 70Gy (lapatinib, placebo), duration 49 (lapatinib) and 50 days (placebo); median cisplatin dose 260mg/m(2) (lapatinib) and 280mg/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.
U2 - 10.1016/j.ejca.2012.11.023
DO - 10.1016/j.ejca.2012.11.023
M3 - Article
C2 - 23265705
SN - 1879-0852
SN - 1879-2995
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -