Frontline gefitinib in advanced non-small cell lung cancer: Meta-analysis of published randomized trials

Abstract

Objective: Gefitinib, a small molecule tyrosine kinase inhibitor, showed a substantial effect as a salvage treatment for patients with advanced non-small cell lung cancer (NSCLC) who had failed prior chemotherapy. Subsequent phase III trials in previously untreated patients have failed to demonstrate such benefit. It was later reported that gefitinib had a positive outcome when used in selected population.

Rational: The inconsistent results and the lack published meta-analysis that systematically examined the overall efficacy of gefitinib in the frontline setting in such patients, have prompted the current meta-analysis.

Methods: We selected for analysis only those randomized, peer-reviewed clinical studies where the efficacy of gefitinib-based therapy (GBT) was investigated in chemotherapy naïve patients with locally advanced or metastatic NSCLC. We also included studies where patients were randomized between gefitinib vs. placebo or none after initial chemoradiation or chemotherapy induction offered to all included patients.

Results: We identified seven eligible studies involving 2,646 and 1,939 patients randomized to GBT and to control arms, respectively. In mostly unselected population, GBT was not associated with higher objective response rate (ORR), progression-free survival (PFS) (hazard ratio [HR] = 0.97, 95% CI: 0.78-1.20, P = 0.78), or overall survival (OS) (HR = 1.04, 95% CI: 0.95-1.13, P = 0.45) as compared with control interventions. In a fraction of patients with known EGFR mutation status, GBT showed significantly higher ORR among patients with mutant EGFR (odds ratio [OR] = 2.81, 95% CI: 1.71-4.62, P < 0.0001); however, EGFR mutation was not associated with better PFS or OS with GBT. Nevertheless, patients receiving GBT experienced significant improvement in quality of life as compared with those in the control arms.

Conclusion: We conclude that GBT cannot be recommended for frontline management of patients with advanced NSCLC in unselected patient population.

Keywords: EGFR; gefitinib; non-small cell lung cancer.

Figure 1

Odds ratio of objective response rate of GBT vs. control interventions (random effects model). G, Gefitinib

Figure 2

Odds ratio of objective response rate of GBT vs. control interventions according to EGFR mutation status (random effects model). G, Gefitinib

Figure 3

The hazard ratio for progression-free survival of GBT vs. control interventions (random effects model). G; Gefitinib

Figure 4

The hazard ratio for overall survival of GBT vs. control interventions (random effects model). G, Gefitinib

Figure 5

Odds ratio of quality of life assessment of GBT vs. control interventions (random effects model). FACT-L, Functional Assessment of Cancer Therapy-Lung; G, Gefitinib; LCS, Lung–cancer subscale; TOI, Trial outcome index