Induction Chemotherapy with or without Erlotinib in Patients with Head and Neck Squamous Cell Carcinoma Amenable for Surgical Resection

Purpose: Neoadjuvant chemotherapy prior to definitive surgery has been used widely for locally advanced oral squamous cell carcinoma (OSCC). We evaluated neoadjuvant erlotinib with plat-inum-docetaxel versus placebo with platinum-docetaxel in patients with stage III-IVB OSCC. Patients and Methods: Patients with newly diagnosed stage III, IVA, and IVB (American Joint Committee on Cancer 7th) OSCC amenable to surgical resection were included. Patients were ran-domized to receive up to 3 cycles of chemotherapy with concurrent erlotinib or placebo, followed by surgery. The primary endpoint was major pathologic response (MPR) rate; secondary endpoints includ-ed safety, overall survival (OS), and progression-free survival (PFS). Results: Fifty-two patients received at least 1 cycle of treatment and 47 were evaluable with surgical resection. MPR rate was not different between erlotinib (30%, 7/23) and placebo arms (41.7%, 10/24; P = 0.55). At median follow up of 26.5 months, there was no difference on OS or PFS between groups. Patients who received erlotinib with chemotherapy and achieved MPR (n = 7) had no recurrence. The treatment-related adverse event rates were not different between the two groups (96% vs. 96%). However, rash, mostly low grade, was more common in the erlotinib arm (79% vs. 50%). Transcriptomic analysis in the pretreatment samples indi-cated that genes in protein glycosylation and Wnt signaling path-ways were associated with benefit in those treated with erlotinib plus chemotherapy. Conclusions: The addition of erlotinib to platinum-taxane che-motherapy was well tolerated but did not induce higher rates of MPR or PFS or OS survival benefit. Patients who received chemo-therapy with erlotinib and achieved major pathologic responses had excellent clinical outcome.