In a phase II trial reported in The Lancet Oncology, doctors from Dana Farber Cancer Institute http://www.dana-farber.org/ in Boston found that treatment of patients with advanced non–small cell lung cancer (NSCLC) with EGFR mutations or clinical characteristics associated with response to EGFR inhibitors with the targeted pan-HER inhibitor dacomitinib was promising.
A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Targeted therapies are playing an increasing role in the treatment of NSCLC.
Mutations in the epidermal growth factor receptor (EGFR) gene may affect how NSCLC responds to certain drugs. EGFR contributes to the growth of several types of cancer, and drugs like Tarceva® (erlotinib) and Dacomitinib that block the activity of EGFR can slow cancer growth. Dacomitinib is an orally active, highly selective, second-generation small-molecule inhibitor of the pan-epidermal growth factor receptor (EGFR) family of tyrosine kinases (ErbB family) with potential antineoplastic activity. Dacomitinib specifically and irreversibly binds to and inhibits human EGFR subtypes, resulting in inhibition of proliferation and induction of apoptosis in EGFR-expressing tumor cells.
Individuals with EFGR positive NSCLC treated with Tarceva® plus chemotherapy have delayed time to cancer progression and improved survival compared to those treated with chemotherapy alone. Dacomitinib has also been shown to be active in patients previously treated with Tarceva®.
In the current study 89 patients who were never-smokers or former light smokers or had EGFR mutation regardless of smoking status were treated with Dacomitinib in 28-day cycles until cancer progression, unacceptable side effects or withdrawal from the study.
Overall 54% of patients responded to treatment and the average, duration of response was 12.9 months. Dacomitinib was generally well tolerated with minimal side effects and the investigators concluded that Dacomitinib had encouraging clinical activity as treatment in patients with advanced NSCLC likely to have an EGFR mutation.
Reference: Janne P, Ou S-H, Kim D-W, et al. Dacomitinib as first-line treatment in patients with clinically or molecularly selected advanced non-small-cell lung cancer: a multicentre, open-label, phase 2 trial. The Lancet Oncology. Volume 15, Issue 13, Pages 1433 – 1441, December 2014.