In a phase III trial reported in the Journal of Clinical Oncology, Harrington et al found that the addition of concurrent adjuvant lapatinib (Tykerb) to chemoradiation therapy and the use of maintenance lapatinib did not improve disease-free or overall survival in high-risk patients with resected squamous cell carcinoma of the head and neck. Jean Bourhis, MD, PhD, of the University Hospital Centre, Vaud, Switzerland, is the corresponding author of the Journal of Clinical Oncology article.
In this double-blind trial, 688 patients with resected stage II to IVA squamous cell carcinoma of the head and neck with a surgical margin ≤ 5 mm and/or extracapsular extension from 84 sites in 21 countries were randomized beginning in December 2006 to receive chemoradiotherapy (66-Gy total dose and cisplatin at 100 mg/m2 per day on days 1, 22, and 43) plus placebo (n = 342) or lapatinib at 1,500 mg/d before and during chemoradiotherapy
(n = 346) followed by 12 months of maintenance placebo or lapatinib. Disease-free survival on independent review committee assessment was the primary endpoint.
After a median follow-up of 35.3 months, the study was stopped early due to apparent plateauing of disease-free survival events. Median disease-free survival was 53.6 months in the lapatinib group vs not reached in the placebo group on independent review (hazard ratio [HR] = 1.10, P = .45). On investigator assessment, median disease-free survival was 51.5 vs 59.0 months (HR = 1.03, P = .82). There was no significant difference in disease-free survival between treatment groups according to human papillomavirus status.
Median overall survival was not reached in either group. Estimated overall survival was 67.9% vs 66.2% at 36 months 56.6% vs 57.3% at 60 months.
Grade 3 or 4 adverse events occurred in 75% of patients in the lapatinib group vs 67% in the placebo group, with the most common being mucosal inflammation (24% vs 17%) and lymphopenia (23% vs 21%). The most common treatment-related adverse events of any grade in the lapatinib group were diarrhea (28% vs 7%) and rash (24% vs 8%). Serious adverse events occurred in 48% vs 40% of patients, with lymphopenia (5% vs 5%) and mucosal inflammation (5% vs 3%) being the most common.
The investigators concluded: “Addition of lapatinib to chemoradiotherapy and its use as long-term maintenance therapy does not offer any efficacy benefits and had additional toxicity compared with placebo in patients with surgically treated high-risk squamous cell carcinoma of the head and neck.”
The study was supported by GlaxoSmithKline and the Royal Marsden Hospital/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre; GlaxoSmithKline and Novartis funded editorial support. ■
Harrington K, et al: J Clin Oncol 33:4202-4209, 2015.