Phase II pharmacodynamic trial of erlotinib in advanced non-small cell lung cancer (NSCLC) patients previously treated with platinum-based chemotherapy: preliminary results

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7100 Background: Erlotinib is a potent epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor that significantly prolongs survival in 2nd and 3rd-line NSCLC treatment. This ongoing trial aims to identify predictive markers of clinical benefit, to study the effects of erlotinib on EGFR and downstream signaling components, and to estimate response rates to erlotinib, in NSCLC patients who progressed after platinum-based chemotherapy. Methods: All patients underwent tumor biopsy at study entry, and then started treatment with erlotinib 150mg/d p.o. In a subgroup of patients a further biopsy was performed after 6 weeks of erlotinib treatment. Results: As of October 2004, characteristics of the 54 patients included were: median age 56 (range 35–78); sex: male 71%, female 29%; histology: adenocarcinoma 49%, large cell 33%, squamous cell 18%. Of 49 evaluable patients, 5 (10%) achieved partial response (PR), 19 (39%) had stable disease (SD) and 25 (51%) had progression (PD). PRs were observed in 3 females/2 males; in 2 adenocarcinomas/2 large cell/1 squamous cell; and in 2 current/2 former/1 never-smoker. Erlotinib was well tolerated, 70% of patients had grade 1–3 rash and no unexpected toxicities were seen. On analyzing tumor samples from diagnosis, EGFR mutations were found in 2 patients with PR. No mutations were seen in 1 patient with SD or in 5 with PD. The effects of 6 weeks of erlotinib on EGFR pathway were analyzed in 12 patients for whom tumor samples were available both at study entry and after 6 weeks of treatment. After erlotinib treatment, EGFR expression remained unchanged whereas there was a decrease in phosphorylated (p) MAPK (p=0.002) and Ki-67 expression (p=0.033). Additionally, in those patients with clinical benefit there was a decrease in pAKT expression (p=0.08) after 6-weeks of erlotinib treatment. Conclusions: Erlotinib achieves significant clinical benefit in previously-treated NSCLC patients. EGFR mutations are seen in some erlotinib responders. In serial tumor biopsies, erlotinib was shown to decrease levels of pMAPK and Ki-67. Accrual is ongoing to 80 patients and affymetrix analyses are to be performed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Ltd., Roche, Roche Diagnostics GmbH Hoffmann-La Roche Ltd.

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