- 作者：Youngjoo Lee ; Hyae Young Kim ; Soo-Hyun Lee ; Kun Young Lim ; Geon Kook Lee ; Tak Yun ; Ji-Youn Han ; Heung Tae Kim ; Jin Soo Lee
- 关键词：Acquired resistance ; Drug sensitivity ; EGFR tyrosine kinase inhibitor ; Non&ndash ; small-cell lung cancer ; Organ
- 刊名：Clinical Lung Cancer
- 出版年：March, 2014
- 年：2014
- 卷：15
- 期：2
- 页码：145-151
- 全文大小：764 K
Background
In patients with lung cancer acquiring resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), an intrapatient heterogeneity in response to retreatment with EGFR-TKIs remains to be elucidated.Patients and Methods
Records were retrospectively reviewed for 68 patients with advanced non-small-cell lung cancer who received second EGFR-TKIs after systemic progression that followed durable response to the first聽EGFR-TKIs. All tumor lesions identified on radiologic images before second EGFR-TKIs were categorized into organs.聽Tumor response to EGFR-TKIs was assessed per patient and per organ. Mixed response (MR) was defined as the聽coexistence of at least 2 responsive and progressive organs.
Results
Tumor lesions were detected in 244 organs. The response rate (RR) and median time to progression (TTP) to second EGFR-TKIs for patients were 26.5% and 11.6 weeks (95% CI, 8.5-14.7 weeks), and the RR and median TTP for organs were 38.8% and 17.3 weeks (95% CI, 14.8-19.8聽weeks). Of 35 patients categorized to progressive disease, 22 (62.8%) showed MR. Among organs, the RR was highest for the central nervous system (CNS) and lowest for the liver (CNS vs. others vs. liver: 77.8%, 36.9%, 17.6%; P聽< .001). Multivariate analysis confirmed the organ type and prior drug sensitivity at the time of stopping first EGFR-TKIs as predictors for the risk of progression to second EGFR-TKIs in organs.
Conclusions
Intrapatient heterogeneity in response to second EGFR-TKIs is not a rare event. The organ type and prior drug sensitivity at the failure time of first EGFR-TKIs may predict the efficacy of second EGFR-TKIs in individual organs.