The role of second and third line tyrosine kinase inhibitor monotherapy in EGFR wild-type (and unknown mutational status) advanced non-small-cell lung cancer patients: Findings from a retrospective analysis

Abstract

Background: Second-line treatment for advanced non-small-cell lung cancer (aNSCLC) patients includes monotherapy with a third generation cytotoxic drug (CT) or with the tyrosine kinase inhibitor (TKI) erlotinib. These options are the actual standard treatment for EGFR gene wild-type (WT) status, as patients with EGFR mutations achieve greater benefit by the use of TKI in first-line treatment. Some prospective clinical trials and meta- analyses investigated the comparison between CT and TKI in second-line, but data are conflicting. Method(s): We designed a retrospective trial to gather information about TKI sensitivity in comparison with CT. We selected from clinical records data of patients treated with at least 1 line of CT and at least 1 line of TKI. We collected information about age, sex, performance status, comorbidity, smoking status, histotype, metastatic sites, EGFR mutational status, mutation type, treatment schedule, better response and time-to- progression (TTP) for each line of treatment and overall survival (OS). Statistical analysis was performed by MedCalc version 14.12.0. Survival measures and comparisons were evaluated by Kaplan-Meier method. Result(s): We identified 118 patients who met the selection criteria. Mean age 64,63 (range: 32-84). M/F ratio: 73/45. EGFR non-mutated (41 WT and 54 unknown): 95. All these patients received erlotinib as second-line or third- line TKI. Median TTP at second-line: 4 (CT) vs 4 (TKI) months, p = 0,8882, HR: 1,02 (CT vs TKI), 95%CI: 0,65-1,62. Median TTP at third-line: 2 (CT) vs 3 (TKI) months, p = 0,7181, HR: 1,09 (CTvs TKI), 95%CI: 0,61-1,95. Median OS: 19 (third-line TKI) vs 15 (second-line TKI), p = 0,0946, HR: 0,68 (third-line vs second-line TKI), 95%CI: 0,43-1,06. Conclusion(s): This study explores the role of TKI in EGFR non-mutated aNSCLC patients. The data about the comparison of TKI with CT show no difference in TTP for both second-line and third-line treatment. The analysis of OS highlights a trend to a benefit in the group of patients who receive TKI in third-line, even if this result is not statistically significant.