Effects of lapatinib monotherapy: Results of a randomised phase II study in therapy-naive patients with locally advanced squamous cell carcinoma of the head and neck
British Journal of Cancer, 08/21/2011
del Campo JM et al.
–Short-term lapatinib monotherapy did not demonstrate apoptotic changes, but provided evidence of clinical activity in locally advanced SCCHN, and warrants further investigation in this disease.
107 therapy-naive patients with locally advanced SCCHN were randomised (2?:?1) to receive lapatinib or placebo for 2–6 weeks before chemoradiation therapy (CRT)
Endpoints included apoptosis and proliferation rates, clinical response, and toxicity
Versus placebo, lapatinib monotherapy did not significantly increase apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling or caspase-3 assays
Statistically significant decrease in proliferation using Ki67 assay was observed (P=0.030)
In subset of 40 patients that received 4 weeks of lapatinib or placebo, ORR was 17% (n=4/24) vs 0% (n=0/16)
In lapatinib single-agent responders, all had EGFR overexpression, 50% had EGFR amplification, and 50% had HER2 expression by immunohistochemistry (including one patient with HER2 amplification)
These patients showed variable modulation of apoptosis, proliferation, and phosphorylated EGFR on drug treatment
Following CRT, there was statistically non-significant difference in ORR between lapatinib (70%) and placebo (53%)
No clear correlation between changes in apoptosis or proliferation and response to chemoradiation
Mucosal inflammation, asthenia, odynophagia, and dysphagia were most commonly reported AEs with lapatinib
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