NEW YORKThe investigational epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib (Tarceva, also known as OSI-774) produced objective remissions and mild toxicity in stage IV non-small-cell lung cancer (NSCLC) patients who had undergone a number of prior chemotherapy regimens, according to results of a phase II study.
"There is no question that Tarceva is active and well tolerated in heavily pretreated NSCLC patients, all of whom had received previous platinum-based chemotherapy," said Philip Bonomi, MD, director of oncology, Rush Medical College, Chicago. "The responses are relatively durable, and survival is certainly very encouraging."
Rash and diarrhea were common but rarely severe; only a few patients required dose reductions due to adverse events, Dr. Bonomi said at the Mount Sinai School of Medicine Chemotherapy Foundation Symposium XX.
Response to erlo-tinib therapy appeared to correlate with rash; almost every responder developed rash vs only about half of nonresponders. "It may be that the rash has some predictive value in terms of response," he said.
The phase II NSCLC trial was based on preclinical studies showing that inhibiting the EGFR pathway reduces malignant cell proliferation. A high percentage (40% to 80%) of NSCLC tumors express EGFR. "When it first came out, people thought it would be a cytostatic drug, but this agent actually causes tumor regression," Dr. Bonomi said.
To determine the response rate in NSCLC after treatment with a platinum-containing chemotherapy regimen, investigators enrolled 57 patients with at least a low level of EGFR expression and relatively good performance status. Patients received erlotinib 150 mg/d orally, with an opportunity for dose reduction or escalation depending on toxicity. Response was confirmed at 6 weeks, and disease was assessed every 8 weeks.
The 57 study subjects included 23 men and 34 women (mean age, 62 years) who had received at least one prior chemotherapy regimen; all but 10 had received two or more regimens, and all but 2 had received a prior platinum. Median duration of treatment was 63 days (range, 12 to 843) and dose decreases were required in only three patients (5%).