Gefitinib for Epidermal Growth Factor Receptor Mutant Lung Cancers: Searching for a Weapon of Mass Destruction

摘要: In the spring of 2004, association between somatic mutations in epidermal growth factor receptor (EGFR) non– small-cell lung cancer (NSCLC) and sensitivity to EGFR tyrosine kinase inhibitor gefitinib was first described. Since that time, numerous retrospective studies have confirmed these original observations. Patients with treated a 60% 90% chance achieving radiographic partial response median time progression approximately 12 months (Table 1). However, were all observations limited by multiple potential biases including patient selection based on availability tumor material, differences prior treatments, methods mutation detection. addition, other biomarkers associated gefitinib’s clinical benefit, increased copy number expression as detected immunohistochemistry, also emerged over last 2 years. The contribution role remain be definitively determined from ongoing prospective studies. this issue, Inoue et al report trial which chemotherapy-naive advanced NSCLC patients their systemic therapy. They started study June performed mutational analyses 99 (75 assessable), found 25 (33%). frequency is consistent previously published Japanese patients. 16 had rate 75% progression-free survival 9.7 months, same types identified, in-frame deletion exon 19 being most common type Despite small sample size, met its primary protocol-defined end point 70% rate, observation confirms previous associating efficacy gefitinib. What are implications study? findings leave little doubt about predictive value (exon deletions L858R) for after treatment does not address whether will survive longer when compared chemotherapy. This require phase III comparing outcome chemotherapy adding inhibitors population remains evaluated demonstrate feasibility detection routine care NSCLC. more likely than white (30% 10% 15% patients). frequency, combined rapid turn around (median, 7 days) sequencing, clearly helped study. United States or Western Europe, 300 would need screened (rather al) find sufficient material sequencing and, ultimately, obtain similar assessable Nevertheless, suggest may worthwhile effort populations well. population. To date, 20 different been mutations, L858R, still needs al, there four who either stable (n 2) progressive disease respond gefitinib? There no obvious among achieved response. DNA tumors did contain described T790M resistance. Several recent demonstrated that, both mutant cell lines JOURNAL OF CLINICAL ONCOLOGY E D I T O R A L VOLUME 24 NUMBER 21 JULY