A prospective clinical trial to assess lapatinib effects on cutaneous squamous cell carcinoma and actinic keratosis

BACKGROUND: Antiepidermal growth factor receptor (EGFR)-targeted therapy is widely used in many epithelial cancer types. We investigated lapatinib effects on cutaneous squamous cell carcinoma (cSCC) scheduled for resection and in coexisting precursor lesions (actinic keratosis (AK) and Bowen's disease (BD)) in a phase 2 mode of action clinical trial including a histological workup of the cSCC. PATIENTS AND METHODS: We initiated a prospective single-centre, open-label, non-controlled clinical study with translational intentions to investigate changes in size and histopathological features in cSCC after a 14-day period of neoadjuvant lapatinib therapy at a dose of 1500 mg/day prior to surgery, to quantify the impact on AK and BD in the same patient after 56 days and to evaluate the tolerability in patients with cSCC and precursor lesions. RESULTS: 10 immunocompetent male patients were included with a mean age of 73 years (range 59–87). 8 patients were treated with the study medication lapatinib 1500 mg/day for a total duration of 56 days according to the protocol and were available for full analysis, whereas 2 patients had to discontinue treatment during the first 2 weeks because of adverse events (diarrhoea, pancreatitis). Tolerability was acceptable with only 1 related grade III adverse event. A reduction in tumour size of cSCC was documented in 2 of 8 evaluable patients after 14 days of treatment. The mean regression of captured precursor lesions was 30% after 56 days of treatment and 36% 28 days after therapy cessation. CONCLUSIONS: Short-term lapatinib resulted in a cSCC tumour reduction in 2 of 8 patients. In addition, there was a clinically documented reduction of AK in 7 of 8 patients encouraging larger clinical trials, especially in high-risk patients with cSCC such as organ transplant recipients. TRIAL REGISTRATION NUMBER: NCT0166431.