<p>Clinicopathological Characteristics And EGFR-TKIs Efficacies In Lung Squamous Cell Carcinoma Patients Harboring An<em> EGFR</em> Sensitizing Mutation</p>

Abstract

ObjectiveThis study analyzed the relationship between the clinicopathological features and epidermal growth factor receptor (EGFR) mutation status of squamous cell lung cancer (SqCLC) patients. Mutation status was analyzed by comparing the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next-generation sequencing (NGS). We also assessed the efficacies of EGFR tyrosine kinase inhibitors (TKIs).MethodsRetrospective analysis was performed for 292 SqCLC patients treated at the Guangxi Medical University Affiliated Tumor Hospital from December 2013 to December 2018. The EGFR mutations in tumor tissues were identified by ARMS-PCR and NGS. The affiliation between EGFR mutation and clinicopathological features was analyzed. Efficacies of EGFR-TKIs and survival were evaluated using the benchmarks of response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and the Kaplan–Meier method, respectively.ResultsAmong the 292 SqCLC patients, 24 (8.2%) were identified to have an EGFR-sensitizing mutation. Both ARMS-PCR and NGS were equally effective in detecting EGFR mutations. Females and non-smokers had higher EGFR mutation rates than males and smokers (22.1% vs. 5.1%, P = 0.007 and 16.7% vs. 4.5%, P = 0.001, respectively). EGFR mutation was unrelated to the degree of differentiation, clinical stage, specimen type and level of serum carcino-embryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) (P > 0.05). In the 14 EGFR mutant cases treated with EGFR-TKIs, the objective response rate (ORR) and disease control rate (DCR) were 28.6% and 78.6%, respectively. Median progression-free survival (mPFS) and overall survival (mOS) were 4.9 and 10.75 months, respectively, with fine tolerance and mild side-effects.ConclusionEGFR-sensitizing mutations are rare in SqCLC patients with females and non-smokers having a higher risk of harboring them. There was no difference in the detection rates of EGFR for both the ARMS-PCR and NGS methods. EGFR-TKIs showed modest efficacies and low toxicity profiles in EGFR mutant cases.

Epidermal Growth Factor Receptor Mutation Status and Response to Tyrosine Kinase Inhibitors in Advanced Chinese Female Lung Squamous Cell Carcinoma: A Retrospective Study

“…EGFR mutation rate of advanced female lung SCC was 29.9% (46/154) in our data, which was similar to the results of two previous Chinese studies (33.3% and 18.1%, respectively) and was significantly higher than that of male lung SCC (4.0%, 64/1599) ( 10 , 11 ). This phenomenon has been reported in both Chinese (22.2% and 5.1%) and Russian population (14.4% and 1.8%), and EGFR mutation rate of female SCC patients in Russia seems lower than that in Chinese population (14.4% vs. 18.1-33.3%) ( 6 , 45 ).…”

“…The ORR and DCR of the first and second generation TKI for EGFR mutation positive non-squamous non-small cell lung cancer (NSq-NSCLC) were about 56.0%-71.2% and 90.0%-91.7%, respectively (23,47). We found that the ORR and DCR of female patients with lung SCC treated with TKIs were 44.7% and 81.6%, respectively, which were lower than those of NSq-NSCLC, but seemed to be higher than that of patients with SCC (most of them were male patients; ORR:25.0%-31.8%, DCR: 47.3%-81.8%) (7,9,11,13,24). This suggests that although with EGFR mutation, the effect of SCC patients on TKI is not as good as that of adenocarcinoma patients, but the effect of female patients with SCC is better than that of male patients.…”

“…It was said that EGFR mutation in patients with SCC was caused by tumor heterogeneity and the component of mixed adenocarcinoma, especially in small biopsy specimens ( 46 ). However, many studies have confirmed that EGFR mutation really occurs in patients with SCC, whether it is from small biopsy specimens or surgical specimens ( 7 , 11 ).…”

“…So most patients with lung SCC have no chance to get benefit from EGFR tyrosine-kinase inhibitors (TKIs). However, it was found in the subgroup analysis of several studies that among all lung SCC patients, the EGFR mutation rate in female patients seemed to be higher, about 14.4% to 33.3% ( 6 , 10 , 11 , 14 ). But the sample size of female SCC in these studies were very small, and at present there was no specific study on EGFR mutation status in female lung SCC.…”

“…Among all the driving gene mutations, the most common one is epidermal growth factor receptor (EGFR) gene mutation, especially for the patients in east Asia, non-smoking, women and adenocarcinoma (5). Compared with advanced lung adenocarcinoma patients, the EGFR mutation rate of patients with lung squamous cell carcinoma (SCC) is much lower, about 4.2%-23.8% only (6)(7)(8)(9)(10)(11)(12)(13). So most patients with lung SCC have no chance to get benefit from EGFR tyrosine-kinase inhibitors (TKIs).…”