Erlotinib improves survival in stage III non-small cell lung cancer

NEW YORK (Reuters Health) - Both progression-free and overall survival are extended in patients with advanced non-small cell lung cancer treated with erlotinib following standard chemotherapy, according to phase III clinical trial results reported this week.

Erlotinib (Tarceva), which targets epidermal growth factor receptors, is also effective as maintenance therapy following concurrent chemoradiotherapy, investigators also announced in another presentation at the 13th World Conference on Lung Cancer in San Francisco.

As part of the multinational SATURN study, Dr. Federico Cappuzzo, from Instituto Clinico Humanitas in Milan, Italy, and his team tested erlotinib as first-line therapy following non-progression with chemotherapy. Currently, erlotinib is indicated only as a second- or third-line agent.

Of 1949 patients who were enrolled, 889 did not have progressive disease and were therefore randomly assigned to erlotinib (150 mg/d, n = 438) or to placebo (n = 451), Dr. Cappuzzo's team reports in their meeting abstract.

Progression-free survival was significantly prolonged in the erlotinib arm compared with placebo (hazard ratio (HR) 0.71, p = 0.000003), amounting to an increase of about 40%. The abstract did not include absolute survival times.

In a preplanned subgroup analysis, progression free survival was extended the most for never smokers (HR 0.56), and least for current smokers (HR = 0.80).

"The study also met a key secondary endpoint of extending overall survival in patients who received erlotinib immediately after initial chemotherapy. A statistically significant improvement in overall survival was seen in this pre-planned final analysis of the total patient population," the researchers said in a meeting press statement.

A second group, headed by Dr. Wolfram Brugger, from Schwarzwald-Baar Clinic in Villingen-Schwenningen, Germany, studied the effect of EGFR mutation status on outcomes in the same group of patients.

Results showed a marked increase in progression-free survival in patients with EGFR mutations (exons 18-21). One mutation in particular was tested for in 368 patients, was found present in 40. The HR was 0.09 for those with the mutation, compared with 0.81 in those with wild type EGFR (p = 0.0006).

A US research team examined the effectiveness of 2 years of maintenance therapy with erlotinib following concurrent chemoradiotherapy. Of 243 patients originally randomized to the study drug or placebo, 156 were actually treated.

Median time to progression was not reached at the time the meeting abstract was submitted, vs 13.1 months for placebo (p = 0.005).

"The increase in overall survival is brand new information," Dr. Roy S. Herbst told Reuters Health, referring to the work by Dr. Cappuzzo's team. Dr. Herbst, who also presented findings for targeted therapy in the same session, is chief of thoracic medical oncology at the M. D. Anderson Cancer Center in Houston.

Oncologists using erlotinib and other biologic agents for lung cancer will need to "use them in a personalized way," Dr. Herbst said. "Everyone should sequence a patient's tumor for EGFR mutations, so that they can be used as front-line therapy. If you want to maximize treatment and be as effective as possible, those are the people you need to identify up front."

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