Real-World Analysis of Clinical Characters, Prognosis, And Recurrence Pattern: A Retrospective Multicenter Study of 429 Patients with Epidermal Growth Factor Receptor (EGFR) Mutant Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Abstract

Advanced NSCLC with EGFR mutations is a distinct subgroup which has unique biology and a high response rate towards target therapy of EGFR-tyrosine kinase inhibitors (TKIs). However, for EGFR-mutant unresectable LA-NSCLC who treated with conventional chemoradiotherapy (CRT), limited data are available about the relationship between clinical characteristics, prognosis, and subsequent failure patterns. Here we summarized these clinical data using a joint academic center database. We retrospectively collected data for patients with unresectable stage III NSCLC harboring EGFR mutations from nine major academic cancer institutions in China from Jan 2012 to December 2018. Patients with concurrent ALK rearrangements were excluded. Tumor or ctDNA genotyping was performed using polymerase chain reaction amplification or next-generation sequencing method. OS, PFS, local-regional failure free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated from the date of diagnosis. A total of 429 patients met selection criteria were included in the study, among whom 209 (48.7%) patients had exon 19 deletion, 165 (38.5%) had L858R exon, 26 (6.1%) had uncommon mutations, and 29 (6.8%) had multiple mutations. 298 patients (69.5%) were smoker, and 227 (61.9%) were female. The median age was 58 (30-89) years and 230 (53.6%) was younger than 60 years. 296 (69.0%) patients had stage IIIB disease and 285patients (66.4%) with smaller primary lesions (T1/2). Of the 367 patients with survival information, the median follow-up time was 40.8 months. the median OS were 55.5 month (95%CI 43.4-67.5). The 1-, 2-, 3-, and 5-years OS rates are 94%, 79%, 63%, and 47%, respectively. The median PFS was 16.6 months (95%CI 14.9-18.2). The 1-, 2-, 3-, and 5-years PFS rates are 64%, 34%, 22%, and 14%, respectively. There was no difference in OS or PFS by different genotypes. In multivariable analysis, use of EGFR-TKIs (yes v not: HR = 0.56, 95%CI 0.43-0.74, P<0.001) and stage (IIIA v IIIB: HR = 0.67, 95% CI 0.51-0.87, P = 0.003) were independently associated with PFS; and age was independently associated with OS (≥60 v <60 years: HR = 1.45, 95% CI 1.03-2.03, P = 0.035). As for relapse pattern after initial treatment of thoracic radiotherapy (RT) and chemotherapy, 46.5% of patients developed DM, 31.0% developed LRR, and 22.5% developed simultaneous DM and LRR. The incidence of brain metastasis was 24.8% (91 patients). By multivariable analysis, EGFR-TKIs independently increased the DMFS (yes v not: HR 0.51,95%CI 0.37-0.70, P<0.001). To our knowledge this is the largest retrospective analysis of EGFR-mutant LA-NSCLC, aiming to provide a reliable baseline and prognosis estimate. Multivariable analysis demonstrated EGFR-TKIs might independently prolong DMFS. The combined treatment modality of RT and EGFR-TKIs may be promising.