A meta-analysis of adjuvant EGFR-TKIs for patients with resected non-small cell lung cancer

Abstract

Objectives: We performed this meta-analysis to compare adjuvant EGFR-TKIs with a placebo or adjuvant chemotherapy among patients with resected non-small cell lung cancer (NSCLC).

Materials and methods: A literature search was performed using relevant keywords. All randomized controlled trials (RCTs) that compared the survival benefits of adjuvant EGFR-TKIs with those of placebo or adjuvant chemotherapy for resected NSCLC were eligible for inclusion.

Results: The literature search yielded five eligible RCTs including three RCTs that compared adjuvant EGFR-TKIs with a placebo, and two RCTs that compared adjuvant EGFR-TKIs with chemotherapy. For unselected intent-to-treat patients who received adjuvant EGFR-TKIs versus a placebo, the hazard ratio (HR) of disease-free survival (DFS) was 0.88 (95% confidence interval (CI): 0.59-1.32; P = 0.54). For patients with an EGFR mutation, the DFS after adjuvant EGFR-TKIs was superior to that after a placebo, with a HR of 0.59 (95% CI: 0.40-0.88; P = 0.009). For patients with an EGFR mutation, the DFS after EGFR-TKIs was greater than that after chemotherapy, with a HR of 0.42 (95% CI: 0.19-0.93; P = 0.03). For patients with wild-type EGFR, the DFS of adjuvant EGFR-TKIs was similar to the placebo, with a RR of 1.00 (95% CI: 0.62-1.60; P = 0.99). Treatment with EGFR-TKIs resulted in more adverse events compared with the placebo, with a risk ratio (RR) of 2.72, (95% CI: 2.23-3.33; P < 0.00001), but fewer adverse events compared with chemotherapy, with an RR of 0.26 (95% CI: 0.18-0.38; P < 0.00001).

Conclusions: For patients with resected NSCLC harboring EGFR mutations, treatment with an adjuvant EGFR-TKI was superior to that of a placebo or chemotherapy in terms of DFS. Treatment with adjuvant EGFR-TKIs were not effective among patients with wild type EGFR NSCLC.

Keywords: Adjuvant therapy; Dacomitinib; Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI); Erlotinib; Gefitinib; Icotinib; Meta-analysis; Non-small cell lung cancer (NSCLC); Osimertinib; Surgery; Targeted therapy.