Analysis of clinical outcomes according to mutation subtype in EGFR-positive advanced non-small cell lung cancer (aNSCLC) patients treated with EGFR Tyrosine Kinases Inhibitors (TKIs) as first line

Abstract

Background: The correlation between EGFR mutation subtype and efficacy of TKIs in patients with aNSCLC is uncertain. Therefore, TKIs are used regardless of mutation subtype. However, data of literature suggests better outcomes for patients with exon 19 deletions (19del) in comparison with exon 21 point mutations (L858R). Methods: Patients with EGFR-positive aNSCLC receiving TKIs as first line treatment were included in the analysis. Mutational status at diagnosis was detected on tumor tissue or on circulating free tumor DNA (cft-DNA). The association between mutation subtype and clinical factors was assessed by Pearson chi square test, while differences in progression free survival (PFS) and overall survival (OS) according to mutation subtype were evaluated by Log-rank test. Results: Between January 2011 and December 2016 a consecutive series of 39 EGFR-positive patients (all with adenocarcinoma) received a first line TKI: Gefitinib (21 pts), Erlotinib (14 pts) or Afatinib (4 pts). Most of patients, whose median age was 70 years (range 35-84), were female (67%), never smokers (74%) and with stage IV (97%). EGFR mutations were detected on tumor tissue in 37 pts and on cft-DNA in 2 pts. No correlation was found between mutation subtype and site of metastases (lung, lymph nodes, liver, adrenal, bone and brain). After a median follow up of 11.2 mos, the mutation subtype did not influence PFS (median 9.6 mos, 95% CI 3.3– 15.9 for 19del group vs 8.3 mos, 95% CI 6.6 - 9.9 for L858R group) and OS (median 17.4 mos, 95% CI .00 - 34.7 for 19del group vs 18 mos, 95% CI 12.3 - 23.8 for L858R group). Anyway, it is noteworthy that 2-y PFS and OS rates were quite different according to mutation subtype being 24.8% and 36.4% in 19del pts, compared to 0% and 14.8% in L858R pts, respectively. Conclusions: Our analysis showed that TKIs may be used for treating EGFR-positive lung adenocarcinoma regardless of mutation subtype. Despite the small sample size, the mutation subtype did not correlate with site of metastases, and no statistically significant difference was found in terms of PFS and OS between two mutation subtypes.