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
Mené sur 67 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade III/IVA/IVB et non résécable (âge médian : 56 ans), cet essai randomisé de phase II évalue, du point de vue des taux de survie à 18 mois et du grade associé aux événements indésirables, l'efficacité et la toxicité d'une chimioradiothérapie concomitante combinée au lapatinib
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/m2 (lapatinib) and 280 mg/m2 (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.