关键词: 肺腺癌, 表皮生长因子受体酪氨酸激酶抑制剂, T790M, 疗效, 耐药

Abstract:

Objective To prospectively analyze the correlation between the prognosis of lung adenocarcinoma with acquired resistance to the first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and the T790M mutation. Methods A total of 93 eligible patients with lung adenocarcinoma were selected. The EGFR-sensitive mutation and T790M mutation status were detected by the next-generation sequencing (NGS). Osimertinib was used as the EGFR-TKI treatment in the second or third-line treatment, and patients in the control group were given chemotherapy and/or radiotherapy. Objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) of the second and third-line treatment were evaluated.Results The ORR was comparable between lung adenocarcinoma patients with positive or negative T790M mutation ( P=0.084); while a significant difference was detected in the DCR ( P=0.01). There were significant differences in the ORR ( P=0.022) and DCR ( P=0.016) in lung adenocarcinoma patients with positive or negative T790M mutation who were treated with the second-line treatment of osimertinib; similar results were obtained in the third-line treatment of osimertinib as well (ORR [ P=0.016] and DCR [ P=0.011]). The Mann-Whitney U test showed that the mutation status of T790M was significantly correlated with PFS in all lung adenocarcinoma patients ( P<0.01), and those treated with the second-line treatment ( P=0.022) and the third-line treatment ( P=0.016). Kaplan-Meier survival analysis showed that the T790M mutation significantly influenced the overall PFS in lung adenocarcinoma patients ( P<0.01). In the T790M-positive group, there was a significant difference in the PFS between those with EGFR exon 19 mutation and exon 21 mutation ( P=0.05). Multivariate Cox proportional hazards regression analysis showed significant differences in EGFR exon 21 vs exon 19 ( H R=0.551, 95% C I=0.357-0.853, P=0.007), T790M-positive mutation vs T790M-negative mutation ( H R=2.972, 95% C I=1.643-5.379, P<0.01), and tumor diameter ≥5 cm vs tumor diameter <5 cm ( H R=0.575, 95% C I=0.373-0.085, P=0.012). Conclusion The prognosis of T790M mutation-positive lung adenocarcinoma patients is better than that of T790M mutation-negative patients. PFS is comparable in T790M-positive lung adenocarcinoma patients treated with the second or third-line treatment of osimertinib. Advanced lung adenocarcinoma patients with the T790M mutation can be treated with the third-generation EGFR-TKI after the development of first-generation EGFR-TKI resistance.

Key words: lung adenocarcinoma, epidermal growth factor receptor tyrosine kinase inhibitor, T790M, efficacy, drug resistance