In an individual patient data meta-analysis reported in the Journal of the National Cancer Institute, Lee et al found no difference in overall survival for first-line treatment with the first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib (Iressa) or erlotinib (Tarceva) vs chemotherapy in EGFR-mutant advanced non–small cell lung cancer (NSCLC). However, tyrosine kinase inhibitor treatment was associated with prolonged progression-free survival, and the majority of chemotherapy patients crossed over to tyrosine kinase inhibitor treatment after disease progression. James Chih-Hsin Yang, MD, PhD, of the National Taiwan University College of Medicine, is the corresponding author of the Journal of the National Cancer Institute article.
The meta-analysis involved three trials comparing gefitinib and three trials comparing erlotinib vs chemotherapy in patients with newly diagnosed EGFR-mutated (exon 19 deletion [del19] or exon 21 L858R [L858R]) advanced NSCLC using individual patient data that included updated survival outcomes. The analysis included 1,231 patients, 632 of whom received tyrosine kinase inhibitor treatment and 599 of whom received chemotherapy.
Median follow-up was 35.0 months. Median overall survival was 25.8 months in the tyrosine kinase inhibitor group vs 26.0 months in the chemotherapy group (hazard ratio [HR] = 1.01, P = .84). There were also no differences according to the presence of del19 (27.4 vs 25.9 months, HR = 0.96, P =.68) or L858R mutation (24.1 vs 25.9 months, HR = 1.06, P = .59; P = .47 for interaction).
Progression-free survival data were available for 1,227 patients. Median progression-free survival was 11.0 months in the tyrosine kinase inhibitor group vs 5.6 months in the chemotherapy group (HR = 0.37, P < .001), with hazard ratios favoring tyrosine kinase inhibitor treatment in both the del19 (0.28, P < .001) and L858R subgroups (0.49, P < .001). Overall, after disease progression, 73.8% of chemotherapy group patients received tyrosine kinase inhibitor treatment, and 65.9% of the tyrosine kinase inhibitor group received chemotherapy, with no subsequent systemic treatment in 0.6% vs 9.1%. Median overall survival after disease progression was shorter in the tyrosine kinase inhibitor group (12.8 vs 19.8 months).
The investigators concluded: “Despite statistically significant [progression-free survival] benefit, there is no relative [overall survival] advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR-mutated NSCLC. This finding is likely due to the high rate of crossover at progression.”