FIRST LINE ERLOTINIB INFERIOR IN UNSELECTED NSCLC PATIENTS 

NEW YORK (Reuters Health) Jul 23 - Switching the usual sequence of therapies yielded poorer results in a recent study of patients with advanced non-small-cell lung cancer and EGFR wild-type tumor.

The usual approach is to give cisplatin-gemcitabine followed by erlotinib. In the TORCH trial, an unselected group of patients received first-line erlotinib followed at progression by cisplatin-gemcitabine.

As Dr. Cesare Gridelli, who led the trial, told Reuters Health by email, the result "confirms that first-line treatment with erlotinib is not a reasonable choice for a general unselected patient population with advanced non small cell lung cancer where chemotherapy should be considered the standard treatment."

On the other hand, he added, his study showed that when tumors do harbor an activating EGFR mutation, then front-line erlotinib should be standard.

Dr. Gridelli of Azienda Ospedaliera S.G. Moscati, Avellino, and colleagues noted in a paper online July 9 in the Journal of Clinical Oncology that although erlotinib is an EGFR tyrosine kinase inhibitor (TKI), the study was launched without any agreement on patient selection. ("Erlotinib was registered for unselected patients," they wrote.)

And in at least one earlier trial, efficacy seemed to be independent of most clinical and biologic factors.

In this setting, the researchers randomly assigned 760 unselected patients to erlotinib followed at progression by cisplatin-gemcitabine or to the standard sequence of first-line chemotherapy followed by erlotinib.

At a median follow-up of 24.3 months there were 273 deaths in the experimental group and 263 in the control group. The median for overall survival, however, was 11.6 months on the standard protocol and 8.7 months in the study group. At a planned interim analysis, the researchers stopped the trial.

EGFR status made a difference, though. Among patients with EGFR mutations, the response rate after first-line treatment was 25.0% with chemotherapy and 42.1% with erlotinib.

And the first progression-free survival analysis showed a "higher efficacy of erlotinib in the presence of EGFR mutation and higher efficacy of chemotherapy in the case of EGFR wild-type tumor."

"EGFR-TKIs," the researchers conclude, "can be used as first-line treatment in patients with tumors harboring EGFR mutations" but the approach is not recommended in unselected patients.

SOURCE: http://bit.ly/MDccPS

J Clin Oncol 2012.