Continuous EGFR tyrosine kinase inhibitor treatment with or without chemotherapy beyond gradual progression in non-small cell lung cancer patients

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Abstract
Background: Several clinical studies have demonstrated that continuous administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could provide additional survival benefit for advanced non-small cell lung cancer (NSCLC) patients who had benefited from prior EGFR TKI therapy. However, whether EGFR TKI combined with chemotherapy could further prolong survival in patients with gradual progression is still unclear. The present study was conducted to evaluate the clinical outcome of continuous EGFR TKI treatment in combination with chemotherapy (combination group) versus continuous EGFR TKI treatment only (monotherapy group) in such a clinical setting. Methods: We designed a cohort study to collect all chart data of NSCLC patients treated with EGFR TKI in our institution from February 2012 to December 2015 retrospectively and followed up the clinical outcome of EGFR TKI monotherapy or therapy in combination with chemotherapy until April 2017 prospectively. All eligible patients had to meet the criteria of gradual progression. The time interval of progression-free survival 1 (PFS1, gradual progression or death) to PFS2 (off-EGFR TKI progression), and overall survival (OS) between the above 2 groups were used in survival analysis. Results: In all, 50 patients were included in our study. Patients’ baseline characteristics were well balanced. Exon 19 deletion mutations and L858R point mutations were detected in 16 and 8 patients, respectively. Twenty, 22, and 8 patients were treated with EGFR TKI in the first, second, and third line setting, respectively. The time interval from PFS1 to PFS2 was 92 and 37 days (monotherapy vs combination), respectively (hazard ratio [HR] =1.16, 95% confidence interval [CI]: 0.61–2.21, P=0.652). The median OS in the monotherapy group and combination group was 696 and 799 days, respectively (HR =0.74, 95% CI: 0.33–1.71, P=0.501). There were no statistical differences between the 2 groups in terms of the time interval from PFS1 to PFS2 and OS. Conclusion: Our results suggested that compared with EGFR TKI monotherapy, its combination with chemotherapy beyond gradual progression may not confer a significant survival benefit to NSCLC patients. Further prospective studies are warranted to reinforce the results of the study.

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