Erlotinib associated with increased OS, PFS in NSCLC with EGFR mutations

According to data from a prospective study, screening patients with non-small cell lung cancer for epidermal growth factor receptor mutations for selection of erlotinib therapy improved median OS and PFS.

The study, conducted by the Spanish Lung Cancer Group, included 2,105 patients with advanced NSCLC from 129 institutions in Spain. All patients were screened for EGFR mutations; 350 patients (16.6%) with mutations were eligible for treatment with erlotinib (Tarceva, OSI Pharmaceuticals) 150 mg daily until progression or intolerable adverse events. Median follow-up was 14 months.

Mutations were detected more frequently in women (69.7%), patients who never smoked (66.6%) and those with adenocarcinomas (80.9%), according to the researchers. Two hundred and seventeen patients received erlotinib; 197 were evaluable.

Among evaluable patients, 24 had a complete response and 115 had a partial response. Deletions in exon 19 were associated with a better response compared with L858R mutations (OR=3.08; 95% CI, 1.63-5.81) and age between 61 and 70 (OR=2.55; 95% CI, 1.32-4.96), according to the researchers.

Median OS was 27 months (95% CI, 22.7-31.3). Median PFS was 16 months (95% CI, 12.7-19.2) in women and 9 months (95% CI, 6.1-11.9) in men. Performance status, age, first-line therapy vs. second-line or third-line therapy, smoking history, or type of mutation were not associated with significant differences in PFS.

In a multivariate analysis, however, the researchers did report an association between poor PFS and male sex (HR=2.94; 95% CI, 1.72-5.03) and L858R mutation (HR=1.92; 95% CI, 1.19-3.10). ECOG performance status of 1, male sex, L858R mutation and bronchioloalveolar adenocarcinoma were associated with poor prognosis in a multivariate analysis of OS.

Mild rashes and diarrhea were the most common adverse events.

Despite the possible future of personalized medicine, the concept is still in its early stages, according to Adi F. Gazdar, MD, Hamon Center for Therapeutic Oncology Research at Simmons Cancer Center and W. Ray Wallace Distinguished Chair in Molecular Oncology Research in the department of pathology at the University of Texas Southwestern Medical Center, author of an accompanying editorial.

“Clearly, we have to develop better drugs, learn how to combine individual targeted therapies with others and with cytotoxic agents, and overcome resistance,” he wrote. “However, the plethora of targets that are presented by cancer cells and the large number of agents currently in clinical trials or being developed offer the promise of a bright future for cancer therapy.”

Rosell R. N Engl J Med. 2009;361:958-967.