SAN FRANCISCO–Maintenance therapy with erlotinib (Tarceva) in patients with non-small-cell lung cancer following chemotherapy provided a statistically significant improvement in survival, according to results from the SATURN trial.
The final results of the phase III SATURN (Sequential Tarceva in Unresectable NSCLC) study found that the median overall survival (OS) for patients treated with erlotinib after chemotherapy was about 12 months vs 11 months for patients who were not treated with the EGFR inhibitor (abstract A2.1).
The difference represented a 19% reduction in the risk of cancer progression (P = .0088), said Federico Cappuzzo, MD, professor of medical oncology at Instituto Clinico Humanitas, Rozzano, Italy.
Dr. Cappuzzo noted that at 30 months, about 20% of patients who were on erlotinib maintenance were still alive compared with about 10% of patients who had not received the sequential treatment.
The overall survival data was a key secondary endpoint (see page 5). The use of erlotinib following chemotherapy resulted in a 29% reduction in the risk of disease progression (P < .0001). "The tolerability profile was consistent with the previous trials and we saw no new safety signals," Dr. Cappuzzo said during the 2009 World Conference on Lung Cancer.
SATURN enrolled 1,949 patients, 889 of whom did not have progressive disease following four cycles of chemotherapy. The researchers randomly assigned 438 patients to 150 mg/day of erlotinib while another 451 patients were assigned to placebo. "The results of this study broaden the patient population for whom erlotinib can be effective," Dr. Cappuzzo said.
A second analysis of SATURN found that specific cancer biology did not seem to affect treatment with erlotinib. "KRAS mutations are a strong negative prognostic factor, but do not have any predictive value for erlotinib therapy. There is no detrimental effect of erlotinib maintenance on patients with KRAS-mutated tumors," said Wolfram Brugger, MD, PhD, from the Schwarzwald-Baar Clinic, University of Freiburg in Germany (abstract B9.1).
Dr. Brugger reviewed the outcomes of the 889 NSCLC patients who had not progressed immediately after initial chemotherapy consisting of four cycles of platinum-based doublet. He evaluated EGFR protein and EGFR gene copy number, EGFR and KRAS mutations, and EGFR polymorphism in order to potentially identify predictive markers for erlotinib therapy.
The researchers observed that the use of erlotinib provided a clinical benefit in terms of both PFS and OS for all patients, regardless of the status of biomarkers. "These data suggest that the OS difference is not driven by EGFR mutation and that none of the biomarkers analyzed have adequate predictive power for selection of patients to receive erlotinib maintenance," he said.
Dr. Brugger noted that patients with EGFR wild-type status achieved a significant benefit in reducing the risk of progression of disease by 23% (P = .0243) while no significant benefit was seen among patients with EGFR mutations. However, 67% of the patients identified with wild-type mutations received second-line tyrosine kinase inhibitor treatment that may have confounded the survival analysis. SATURN demonstrated the potential for erlotinib as an effective tool physicians can use to maintain a cancer-free state in their patients, Dr. Brugger said.
