EGFR mutational status in determining choice of TKIs or standard chemotherapy for patients with advanced non-small cell lung cancer

Abstract

Background: Tyrosine Kinase Inhibitors are important therapeutic resources for Non-Small Cell Lung Cancer (NSCLC) patients (pts) expressing EGFR-activating mutations (EGFR-m). However, pts without EGFR-addicted tumors do not display the same benefit. Nevertheless, Erlotinib can currently be prescribed to NSCLC pts after failure of a first-line treatment regardless of their EGFR status. Material (patients) and methods: We retrospectively analysed 143 pts diagnosed with advanced NSCLC between 2005 and 2016 and followed in two different Oncology Divisions. Sixty-nine pts presented EGFR-m while 74 displayed wild-type (WT) EGFR. We initially compared the Progression Free (PFS) and Overall Survival (OS) of the EGFR-m population according to it’s therapeutic sequence i.e. TKIs as first line followed by chemotherapy at progression versus first line chemotherapy followed by anti-EGFR TKIs in second line. We then analysed the PFS and OS of EGFR-wt pts treated with conventional chemotherapy or Erlotinib after failing a standard platinum doublet as first line. Results: In EGFR-m pts median PFS was 11 months in the TKI group and 6 months in those receiving chemotherapy (HR 0.59 CI 95% 0.34-1.04; p = 0.01). However, OS was similar in the two arms: 21 months among pts receiving TKIs in first line and 26 months in pts receiving chemotherapy as first line (HR 1.24, CI 95% 0.69-2.22; p = 0.31). In the EGFR-wt group, median PFS after second line was 5 months in the standard chemotherapy arm and 3 months in the Erlotinib arm (HR 0.76, CI 95% 0.45-1.30; p = 0.01). Differences in the two groups were also significant for OS (26 months among pts receiving chemotherapy and 19 months for those receiving Erlotinib in second line HR 0.67, CI 95% 0.40-1.14; p 0.05). Conclusions: Our study confirms, in an unselected Sicilian population, that EGFR mutations are a strong predictor of TKI benefit. Hence, EGFR-m pts should receive a TKI as first-line treatment as this was associated with improved PFS, although we observed no differences in OS. Moreover, this study suggests the importance of second line standard chemotherapy in subjects with wild-type EGFR since, in this population, TKIs generate inferior responses in terms of both PFS and OS.