MA08.05 Depth of Response to First-Line EGFR TKI Does Not Predict Survival in EGFR-Mutated NSCLC Patients

Abstract

The association between depth of response to EGFR TKI and prognosis of EGFR-mutated NSCLC remains unclear. We aimed to assess the correlation between maximal tumor shrinkage and survival in patients treated with gefitinib and afatinib. Patients with advanced EGFR-mutated NSCLC enrolled in first-line gefitinib and afatinib clinical trials between 2005 and 2014 at the National Taiwan University Hospital were reviewed. Patients who had at least one measurable target lesion that shrank during treatment were included. Overall survival (OS) was defined as time from date of enrollment to death or May 30th, 2016. Correlation between tumor shrinkage and OS was analyzed by Pearson correlation coefficient and Kaplan-Meier method. The influence of high maximal tumor shrinkage (defined as ≥50% tumor shrinkage), age, gender, types of EGFR mutation, central nervous system (CNS) involvement at diagnosis, CNS as site of progression, first-line EGFR TKI (gefitinib or afatinib), and subsequent treatments (chemotherapy, third-generation TKI) on OS was evaluated by a multivariate Cox proportional hazard model. A total of 189 trial patients were screened and 91 patients were eligible for analysis (gefitinib n=42, afatinib n=49). The median maximal tumor shrinkage during first-line EGFR TKI treatment was 53% (interquartile range 30.5%). Maximal tumor shrinkage did not correlate with OS in all patients (R2=0.0225, p=0.169), and either the gefitinib (R2=0.0036, p=0.689) or afatinib (R2=0.0625, p=0.085) group (Fig.1A). High maximal tumor shrinkage also did not significantly affect OS (HR 0.86, 95% CI 0.54-1.40, p=0.564) (Fig. 1B). In multivariate analysis, CNS as site of progression (HR 2.96, 95% CI 1.39-6.29, p=0.005) and first-line afatinib (HR 0.51, 95% CI 0.29-0.91, p=0.022) were the only factors that significantly influenced OS. The depth of response to first-line gefitinib and afatinib was not predictive of OS in patients with EGFR-mutated NSCLC.