TIME FOR FINDING THE TARGET?

EGFR Mutations in NSCLC Predict Better Response to Erlotinib

Roxanne Nelson

Medscape Medical News 2008. © 2008 Medscape

September 13, 2008 (Stockholm, Sweden) — The best responses to customized therapy with erlotinib in patients with non-small-cell lung cancer (NSCLC) are seen in those who have mutations in epidermal growth-factor receptor (EGFR), according to data presented here at the 33rd European Society for Medical Oncology Congress.

"For the first time in lung cancer management, doctors are able, by testing EGFR mutations, to identify a subgroup of patients who can [reach] a new survival landmark in advanced non-small-cell lung cancer with oral EGFR inhibitors, like erlotinib," study author Rafael Rosell, MD, chief of the medical oncology service and scientific director of oncology research at the Catalan Institute of Oncology in Barcelona, Spain, told journalists.

EGFR-mutant ''oncogene-addicted'' cancers have been shown to be a distinct form of NSCLC, and can be targeted with erlotinib. In this study, researchers from the Spanish Lung Cancer Group evaluated the benefits of treatment for NSCLC, customized on the basis of EGFR mutations, in the largest clinical trial to date examining the role of mutations in this population.

Between April 2005 and December 2007, Dr. Rosell and colleagues obtained tumor biopsies from 2312 patients with stage 4 NSCLC that were subsequently screened for the EGFR exon 19 D746-750 deletion and exon 21 L858R mutation. Of this group, 307 had EGFR mutations and were selected for erlotinib therapy.

Data available for 165 of these patients showed that 48 (29.1%) were male and 112 (67.9%) had never smoked. Within this subgroup, 124 (75.2%) had adenocarcinoma, 103 (62.8%) had an exon 19 deletion, and 62 (37.6%) had an exon 21 L858R mutation. Approximately half the patients (53.9%) were receiving erlotinib as first-line therapy, and 46.1% were receiving erlotinib as second-line therapy.

The mean survival was 22 months, based on data from 193 patients, and was more pronounced in women. Mean survival was 28 months for women and 17 months for men. The mean time to progression was 12 months, and was also longer in women than in men.

A response to treatment was observed in 128 patients (70.8% of the cohort) and, of this group, 24 (13.3%) experienced a complete response. The probability of achieving a response was twice as high in patients 61 to 71 years old as in other age groups, and in patients with the exon 19 deletion. Overall survival averaged 27 months for patients with the exon 19 deletion and 16 months for those with the L858R mutation (P = .03)

"Non-small-cell lung cancers with EGFR mutations display a 2- to 3-fold increment in outcome in comparison with non-small-cell lung cancers treated with chemotherapy, in which median survival is 11 months, time-to-progression is 5 months, and response is 20% to 30%," said Dr. Rosell.

Researchers have been studying predictors of response to erlotinib; these include smoking history, histology, race, sex, and mutations, explained Michael H. Cullen, MD, FRCP, a consulting oncologist at Queen Elizabeth Medical Centre, in Birmingham, United Kingdom.

"Only a small proportion of the total patient population had mutations," said Dr. Cullen, who served as discussant for the paper. "It is thus unclear whether the results are mutation-specific predictors, nonspecific predictors, or just prognostic factors."

The Spanish Lung Cancer Group has initiated the European Randomized Trial of Tarceva vs Chemotherapy (EURTAC) for patients with stage 4 NSCLC, to clarify the prognostic and predictive relevance of EGFR mutations.