Survival outcomes and prognostic factors of lung cancer patients with the exon 14 skipping mutation: A single-center real-world study.

INTRODUCTION

The exon 14 skipping ex14) mutation is an important oncogenic driver in lung cancer. We performed a retrospective analysis of clinical data from lung cancer patients with the ex14 mutation to analyze their survival outcomes and associated prognostic factors.

METHODS

A one-step reverse transcription-polymerase chain reaction to examine the presence of the ex14 mutation was performed using RNA samples from 1374 lung cancer patients with no detected and mutations. Pathological features and immunohistochemistry (IHC) results for c-MET were analyzed in patients with ex14-positive tumors.

RESULTS

ex14 was identified in 69 patients with lung cancer, including 53 adenocarcinoma (ADC) and 16 non-ADC patients. In comparison with patients without the ex14 mutation, lung cancer patients harboring the ex14 mutation were generally elderly individuals, never-smokers, and had poor performance scores. A higher frequency of ex14 mutations was detected in pulmonary sarcomatoid carcinoma (PSC) patients (24.3%, n = 9/37). However, stage IV PSC patients with or without the ex14 mutations showed similarly poor overall survival (OS) ( = 0.429). For all 36 ex14-positive lung ADCs, multivariate analysis showed several poor prognostic factors, including strong c-MET IHC staining ( = 0.006), initial brain metastasis ( = 0.005), and administration of only supportive care ( < 0.001). After excluding seven patients who received only supportive care, we further analyzed 29 stage IV lung ADC patients with ex14 mutations who received anti-cancer treatment. Multivariate analysis showed that pemetrexed treatment ( = 0.003), lung radiotherapy ( = 0.020), initial brain metastasis ( = 0.005), and strong c-MET IHC staining ( = 0.012) were independent prognostic factors for OS in these patients.

CONCLUSIONS

A higher frequency of ex14 mutations was detected in PSC patients. Stage IV PSC patients with or without the mutations had similarly poor overall survival. Pemetrexed-based chemotherapy, strong c-MET ICH staining, initial brain metastasis, and lung radiotherapy, may help predict survival outcomes in patients with advanced lung ADCs harboring the ex14 mutation.