NEW YORK (Reuters Health) – The tyrosine kinase inhibitor gefitinib is more effective than standard therapy with carboplatin-paclitaxel for lung adenocarcinomas with mutations in the epidermal growth factor receptor gene (EGFR).

Furthermore, screening for EGFR mutations in patients with lung cancer is feasible and can inform treatment decisions.

These findings are the results of two studies reported in the August 19th Online First issue of The New England Journal of Medicine.

On the basis of encouraging results from uncontrolled studies, Dr. Tony S. Mok, from the Chinese University of Hong Kong and colleagues decided to test gefitinib against carboplatin-paclitaxel in 1217 patients who were nonsmokers or former light smokers. The subjects were randomized to receive gefitinib 250 mg/day or carboplatin/paclitaxel at standard doses.

At 12 months, the rates of progression-free survival in the gefitinib and control groups were 24.9% and 6.7%, respectively. Subjects treated with gefitinib were 26% less likely to experience disease progression or death than were controls (p < 0.001). Among patients with a mutation in EGFR, gefitinib therapy reduced the risk of disease progression or death by 52% (p < 0.001). By contrast, in subjects without EGFR mutations, carboplatin-paclitaxel was more effective, with gefitinib increasing the odds of progression or death by 185%. Side effects were common with both treatment regimens. Rash or acne and diarrhea were the most common with gefitinib, while neurotoxic effects, neutropenia, and alopecia were the most common with carboplatin-paclitaxel. In the second study, Dr. Rafael Rosell, from Hospital Germans Trias i Pujol in Badalona, Spain, and colleagues analyzed data from 2105 patients with advanced non-small-cell lung cancer to assess the feasibility of screening for EGFR mutations and to examine the association with erlotinib response. Overall, 16.6% of patients had EGFR mutations. Correlates of EGFR mutation positivity included female gender (69.7%), never smoker status (66.6%), and adenocarcinoma (80.9%). Roughly 62% of the mutations were deletions in exon 19 and 38% were the L858R mutation. In 217 patients treated with erlotinib, the median rates of overall and progression-free survival were 27 and 14 months, respectively. Progression-free survival was 2.94-times more likely in men than in women, 1.92-times more likely with the L858R mutation than with exon 19 deletions, and 1.68-times more likely with the L858R mutation versus no mutation. As with gefitinib, rashes and diarrhea were the most common side effects with erlotinib, the report indicates. In a related editorial, Dr. Adi F. Gazdar, from the University of Texas Southwestern Medical Center, Dallas, discusses EGFR inhibition for lung cancer in the broader context of individualized treatment approaches. “Personalized medicine is still in its infancy,” Dr. Gazdar writes. “However,” he adds, “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.” Reference:
N Engl J Med 2009.