Comprehensive investigation of oncogenic driver mutations in Chinese non-small cell lung cancer patients

Abstract

PurposeTo determine the frequency of driver mutations in Chinese non-small cell lung cancer (NSCLC) patients.MethodsComprehensive mutational analysis was performed in 1356 lung adenocarcinoma, 503 squamous cell carcinoma, 57 adenosquamous lung carcinoma, 19 large cell carcinoma and 8 sarcomatoid carcinoma. The effect of EGFR tyrosine kinase inhibitors (TKIs) on EGFR-mutated lung adenocarcinoma patients after disease recurrence was investigated.ResultsMutations in EGFR kinase domain, HER2 kinase domain, KRAS, BRAF, ALK, ROS1 and RET were mutually exclusive. In lung adenocarcinoma cases “pan-negative” for the seven above-mentioned driver mutations, we also detected two oncogenic EGFR extracellular domain mutations (A289D and R324L), two HER2 extracellular and transmembrane domain mutations (S310Y and V659E), one ARAF S214C mutation and two CD74-NRG1 fusions. Six (1.2%) FGFR3 activating mutations were identified in lung squamous cell carcinoma (five S249C and one R248C). There were three (15.8%) EGFR mutations and four (21.1%) KRAS mutations in large cell carcinoma. Three (37.5%) KRAS mutations were detected in sarcomatoid carcinoma. In EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence, treatment with EGFR TKIs was an independent predictor of better overall survival (HR = 0.299, 95% CI: 0.172–0.519, P < 0.001).ConclusionWe determined the frequency of driver mutations in a large series of Chinese NSCLC patients. EGFR TKIs might improve the survival outcomes of EGFR-mutated lung adenocarcinoma patients who experienced disease recurrence.

EGFR tyrosine kinase inhibitors versus chemotherapy as first-line therapy for non-small cell lung cancer patients with the L858R point mutation

“…EGFR mutations can also be detected in nonadenocarcinoma. Specifically, several previous reports have shown that EGFR mutations can be detected in 35.1–44.0%, 3.9–10.0%, and 11.5–14.3% of patients with adenosquamous carcinoma, squamous cell carcinoma and large cell carcinoma, respectively232425. The results of our prospective multicenter study (IGNITE study) demonstrated that in an Asian population with lung squamous cell carcinoma, the EGFR mutation frequency was 10%26.…”

Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma lung cancer patients harboring EGFR-sensitizing mutations in China

“…EGFR mutation testing was established as an essential part of standard care for adenocarcinoma of the lung but not for non-adenocarcinoma. In recent years, several prospective and retrospective studies have demonstrated that epidermal growth factor receptor mutations can be detected in 35.1-44.0, 3.9-10.0, and 11.5-14.3 % of ASC, SCC, and LCLC, respectively (Wang et al 2015;Kang et al 2007;Zhang et al 2015a, b, c;Rosell et al 2009;Han et al 2015), frequencies that were much higher than expected. A retrospective study demonstrated that EGFR TKIs showed efficacy in EGFR-mutated non-adenocarcinoma patients, but not in EGFR wild-type patients (Fang et al 2013).…”

“…SCC and LCLC patients probably have a minor adenocarcinomatous component that was undetected due to the limitation of the small diagnostic biopsy. This may also explain the relatively higher frequency of EGFR mutations in the ASC population compared with the SCC and LCLC patients (Wang et al 2015;Kang et al 2007;Zhang et al 2015a, b, c;Rosell et al 2009;Han et al 2015).…”

Efficacy of epidermal growth factor receptor inhibitors in combination with chemotherapy in advanced non-small cell lung cancer: A meta-analysis of randomized controlled trials

“…These sensitive mutations are found in approximately 10% of Western patients and 63.1% of Chinese patients with NSCLC [5–7]. Several randomized controlled trials that enrolled patients harbouring EGFR-activating mutations demonstrated that EGFR-TKI is superior to chemotherapy in terms of progression-free survival (PFS) and objective response rate (ORR) [8–11].…”