Yiliang Zhang1,2, Yuan Ma1,2, Yuan Li3,2, Xuxia Shen3,2, Yongfu Yu4, Yunjian Pan1,2, Yang Zhang1,2, Su Yu1,2, Difan Zheng1,2, Yue Zhao1,2, Hong Hu1,2, Yihua Sun1,2, Yawei Zhang1,2, Jiaqing Xiang1,2, Haiquan Chen5,6. 1. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China. 2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 3. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. 4. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China. hqchen1@yahoo.com. 6. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. hqchen1@yahoo.com.
Abstract
INTRODUCTION: Evidence shows that exon 19 deletions (19del) and exon 21 Leu858Arg point mutation (L858R) of EGFR are different in response to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in advanced lung cancers. However, the impact of the two mutational types in the early stage lung adenocarcinoma is unknown. METHODS: We enrolled consecutive patients with operable adenocarcinoma which harbored 19del or L858R to investigate the clinicopathologic characteristics and prognostic outcomes. RESULTS: Between 2008 and 2013, a total of 607 patients with 19del (47.9%) or L858R (52.1%) were included in this study. Clinicopathologic and disease-associated factors were well-balanced between 19del and L858R patients. Both recurrence-free survival (5-year RFS: 37.9% vs. 42.9%, p = 0.075) and overall survival (5-year OS: 64.7% vs. 60.7%, p = 0.741) were similar between the two groups. After relapse, 19del was associated with a better post-recurrence survival (PRS) than L858R (p = 0.016). Multivariate analysis demonstrated that mutational types (HR = 1.521, 95% CI: 1.106-2.093, p = 0.01) and tyrosine kinase inhibitors (TKI) use after recurrence (HR = 0.422, 95% CI: 0.301-0.592, p < 0.001) were independent predictors of PRS. The 19del and L858R patients were similar regarding recurrent patterns, except on pleural/chest wall metastasis (26.0% vs. 12.2%, p = 0.007). CONCLUSIONS: Patients with the early stage lung adenocarcinoma harboring either 19del or L858R share similar RFS and OS. After recurrence, both could benefit from TKI therapy without the need for a second biopsy, but 19del seemed to be associated with better PRS.
INTRODUCTION: Evidence shows that exon 19 deletions (19del) and exon 21 Leu858Arg point mutation (L858R) of EGFR are different in response to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in advanced lung cancers. However, the impact of the two mutational types in the early stage lung adenocarcinoma is unknown. METHODS: We enrolled consecutive patients with operable adenocarcinoma which harbored 19del or L858R to investigate the clinicopathologic characteristics and prognostic outcomes. RESULTS: Between 2008 and 2013, a total of 607 patients with 19del (47.9%) or L858R (52.1%) were included in this study. Clinicopathologic and disease-associated factors were well-balanced between 19del and L858Rpatients. Both recurrence-free survival (5-year RFS: 37.9% vs. 42.9%, p = 0.075) and overall survival (5-year OS: 64.7% vs. 60.7%, p = 0.741) were similar between the two groups. After relapse, 19del was associated with a better post-recurrence survival (PRS) than L858R (p = 0.016). Multivariate analysis demonstrated that mutational types (HR = 1.521, 95% CI: 1.106-2.093, p = 0.01) and tyrosine kinase inhibitors (TKI) use after recurrence (HR = 0.422, 95% CI: 0.301-0.592, p < 0.001) were independent predictors of PRS. The 19del and L858Rpatients were similar regarding recurrent patterns, except on pleural/chest wall metastasis (26.0% vs. 12.2%, p = 0.007). CONCLUSIONS:Patients with the early stage lung adenocarcinoma harboring either 19del or L858R share similar RFS and OS. After recurrence, both could benefit from TKI therapy without the need for a second biopsy, but 19del seemed to be associated with better PRS.
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