Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients

Abstract

Background:We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes.Methods:A cohort of patients with EGFR mutant advanced NSCLC was identified (N=293); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association.Results:Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI=1.21–2.07, P=0.0008), longer TTF (hazard ratio 0.80, 95% CI=0.68–0.92, P=0.003) and better OS (hazard ratio 0.81, 95% CI=0.67–0.99, P=0.04). However, even in patients with ⩽5% mutation fraction, response rate was 34%. Females had longer TTF (P=0.02).Conclusions:EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations.

Analyzing EGFR mutations and their association with clinicopathological characteristics and prognosis of patients with lung adenocarcinoma

“…To date, >30 mutations of EGFR have been reported, including 19-Del (~45% all EGFR mutations), L858R (~40–45%), G719X (~5%), 20-Ins (~1%) ( 5 , 12 , 21 ). Studies have suggested that EGFR mutation rates in patients with lung adenocarcinoma differ among countries and ethnicities, between sexes, and with smoking status ( 25 – 27 ). The overall mutation rate of EGFR in Chinese patients with lung adenocarcinoma in the present study was 50.7%, which is consistent with previous reports ( 6 , 25 – 27 ).…”

“…Studies have suggested that EGFR mutation rates in patients with lung adenocarcinoma differ among countries and ethnicities, between sexes, and with smoking status ( 25 – 27 ). The overall mutation rate of EGFR in Chinese patients with lung adenocarcinoma in the present study was 50.7%, which is consistent with previous reports ( 6 , 25 – 27 ). The mutation rate in female patients was significantly higher than that of male patients (P<0.001) while the mutation rate in smokers was low compared with non-smokers (P=0.003), which was also consistent with previous reports ( 25 , 26 , 28 ).…”

“…Previous studies have revealed that EGFR mutations are predictors of TKI treatment response and prognosis of patients with lung adenocarcinoma ( 10 , 20 , 27 , 29 ). However, clinical studies indicated that patients with different EGFR mutations were associated with different outcomes ( 10 , 29 ).…”

Latency and interval therapy affect the evolution in metastatic colorectal cancer

“…However, our results did not reveal such emergence of RAS mutations in metastatic lesions, possibly due to small sample size. In NSCLC, higher EGFR-mutation allele frequency has been shown to correlate with response to EGFR-tyrosine kinase inhibitors 46,47 . In the event of development of appropriate targeted therapies for KRAS-mutated CRC, our results may have similar relevance.…”

Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine

“…The median progression-free survivals of patients with the ascended type of plasma L858R mutations (L858R increased to its highest level during disease progression) and the stable type (L858R maintaining stable levels during disease progression) were 11.1 (95% CI, 6.6-15.6) and 7.5 months (95% CI, 1.4-13.6), respectively, and the overall survivals (OS) were 19.7 (95% CI, 16.5-22.9) and 16.0 months (95% CI, 13.4-18.5), respectively [97]. Martin et al [98] similarly concluded that the percentages of EGFR mutations in NSCLCs have close associations with the responses to EGFR-TKI therapy, the time to treatment failure (TTF) and the OS. It is supposed that gene amplifications either facilitated the development of gene mutations or amplified their effects [99].…”