Abstract
Both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are widely applied for the treatment of non-small cell lung cancer (NSCLC), but the efficacy of these two treatments in combination is not yet clear. Thus, we sought to evaluate the efficacy of the intercalated combination of these two treatments in NSCLC. The PubMed database, EMBASE, Cochrane Controlled Trials Register, and Chinese Biomedical Database were systematically searched by two researchers for randomized clinical trials (RCTs) that examined the intercalated combination of chemotherapy and EGFR TKIs in NSCLC. Ten studies involving 1,660 patients were included in this systematic review. The statistical results showed that the intercalated combination of chemotherapy and EGFR TKIs significantly improved overall survival (OS) (hazard ratio (HR) = 0.83, 95% confidence interval (CI): 0.70–0.98), progression-free survival (PFS) (HR = 0.65, 95% CI: 0.51–0.84), and the objective response rate (ORR) (risk ratio (RR) = 1.90, 95% CI: 1.22–2.98) compared to chemotherapy alone. Similarly, compared to EGFR TKIs monotherapy, the intercalated combination of chemotherapy and EGFR TKIs seemed superior to EGFR TKIs alone in terms of PFS, ORR and DCR (PFS: HR = 0.75, 95% CI: 0.62–0.91, ORR: RR = 1.49, 95% CI: 1.12–2.00 and DCR: RR = 1.33, 95% CI: 1.15–1.54) in advanced NSCLC therapy.
Highlights
Clinical survival benefit in advanced Non-small cell lung cancer (NSCLC) patients, traditional cytotoxic chemotherapy still plays an important role in the treatment of NSCLC8–10
These four randomized controlled trials (RCTs) included more than 4,000 participants, the results showed that EGFR TKIs combined with chemotherapy synchronously did not improve survival compared to placebo control
The results of this review showed that the intercalated combination therapy pattern, which involves the administration of EGFR TKIs between chemotherapy cycles, prominently increased the survival benefit of the treatment of advanced NSCLC
Summary
Clinical survival benefit in advanced NSCLC patients, traditional cytotoxic chemotherapy still plays an important role in the treatment of NSCLC8–10. Four large-scale phase III randomized controlled trials (RCTs), including INTACT-1, INTACT-2, TALENT, and TRIBUTE, were performed in Europe and the United States since 2004 to evaluate if chemotherapy combined with either gefitinib or erlotinib synchronously as the first-line treatment for advanced NSCLC patients could improve survival[11,12,13,14]. These four RCTs included more than 4,000 participants, the results showed that EGFR TKIs combined with chemotherapy synchronously did not improve survival compared to placebo control. Based on the above clinical trials results, we sought to perform a systematic assessment to verify whether the intercalated combination of chemotherapy and EGFR TKIs is superior to chemotherapy alone or EGFR TKIs alone in the treatment of NSCLC
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