Abstract 419: Presence of pulmonary tuberculosis impair survival in advanced EGFR mutation lung adenocarcinoma patients receiving epidermal growth factor receptor-tyrosine kinase inhibitor
Authors: Xie Yalin , Zhou Wei , Lei An , Huang Zhan , Weiwei Li , Zhu Changbin , Zhu Guanshan , Cen Wenchang 
Published: July 2021

Background Although studies have identified several clinicopathological factors that can predict the response to and survival on epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), few studies have clearly demonstrated the effect of EGFR-TKI in the treatment of patients with underlying pulmonary disease, such as pulmonary tuberculosis (PTB). In addition, cytochrome P450 (CYP) enzyme, CYP3A4, is involved in the metabolism of gefitinib. Previous study reported that in the presence of the anti-tuberculosis drug rifampicin, a potent CYP3A4 inducer, the geometric mean maximum concentration and area under the plasma concentration-time curve of gefitinib were significantly reduced. Thus, we conducted the study to evaluate the impact of PTB on survival for pulmonary adenocarcinoma (PAD) patients that underwent EGFR-TKI treatment.

Methods Clinicopathologic data of PAD patients harboring EGFR mutations from the Guangzhou Chest hospital in China between 2017 and 2019 were reviewed retrospectively. Patients receiving EGFR-TKI treatment were divided into PTB and non-PTB groups. The differences in response to EGFR-TKIs and survival between the two groups were assessed. Formalin-fixed paraffin-embedded (FFPE) tumor tissues were used for the detection of alterations in the EGFR, ALK, ROS1, KRAS, BRAF, RET, MET, HER2, NRAS, and PIK3CA genes.

Results A total of 1448 patients with PAD were reviewed. 223 patients (15.40%) had co-existing PTB, and 317 (21.89%) patients had EGFR-mutated tumors. Among the 223 patients with PTB, 21 (9.42%) harboring EGFR mutations (PTB group). From 296 non-PTB patients with EGFR mutations, 43 patients (non-PTB group) were randomly selected for subsequent analysis. The frequency of former smoker (57.14% vs. 13.95%, p=0.001) and poor performance status (23.81% vs. 6.98%, p=0.007) were significantly higher in the PTB group compared with the non-PTB group. After EGFR-TKIs treatment, the objective response rate (ORR, 58.14% vs.47.62%) as well as disease control rate (DCR, 97.67% vs.85.71) were higher in the non-PTB group than in the PTB group, but there was no statistical difference. In the survival analysis, both the median progression-free survival (PFS, 7.47 months vs. 11.77 months, p=0.038) and the overall survival (OS, 13.00 months vs. 20.00 months, p=0.0017) after EGFR-TKIs were significantly shorter in the PTB group than in the non-PTB group. Secondary data analysis showed that, for patients with 19Del mutation, or metastases sites less than 3, or using first-line EGFR-TKI, EGFR-TKIs treatment significantly prolonged the median PFS and OS in patients without PTB.

Conclusion Presence of PTB may be associated with more frequent former smoker and poor performance status. PAD patients on EGFR-TKI treatment had a worse survival outcome if patients had co-existing PTB.

Citation Format: Yalin Xie, Wei Zhou, An Lei, Zhan Huang, Li Weiwei, Changbin Zhu, Guanshan Zhu, Wenchang Cen. Presence of pulmonary tuberculosis impair survival in advanced EGFR mutation lung adenocarcinoma patients receiving epidermal growth factor receptor-tyrosine kinase inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 419.