Number of metastatic organs negatively affects the treatment sequence in patients with EGFR-TKI failure

Several studies have previously demonstrated the survival benefit of both EGFR-TKI treatment and chemotherapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. The aim of the present study was to clarify the factors influencing the treatment sequence after failure of EGFR-TKI therapy, focusing on the number of organs with metastasis (hereafter, metastatic organs).

Between January 2010 and December 2016, consecutive patients with EGFR-mutated NSCLC who were started on first-line EGFR-TKI were reviewed. The factors influencing withholding systemic chemotherapy and the post-progression survival (PPS) after failure of EGFR-TKI were investigated.

A total of 393 patients were started on first-line EGFR-TKI during the study period. After excluding patients maintained on EGFR-TKI or who received osimertinib targeting secondary EGFR T790M, 297 patients were included in the analysis. Among these, 180 (60.6%) received chemotherapy after failure of EGFR-TKI (TKI-Ct group), while the remaining 117 (39.4%) received no chemotherapy (TKI-only group). Multivariate analysis identified older age (≥75 years: odds ratio [OR] = 0.25, 95% confidence interval [CI]: 0.11-0.43, P < 0.001), poor performance status (PS) (≥2: OR = 0.06, 95% CI: 0.03-0.15, P < 0.001), and three or more metastatic organs (OR = 0.42, 95% CI: 0.22-0.80, P = 0.008) as being significantly associated with withholding of chemotherapy after failure of EGFR-TKI.

A relatively large number of metastatic organs and a poor PS were associated with the withholding of subsequent chemotherapy after failure of EGFR-TKI in EGFR-mutated NSCLC patients. Further research for patients with such a poor prognosis should be investigated in the future.