Frequency and abundance of plasma T790M mutation associated with failure patterns of EGFR-mutant NSCLC treated with tyrosine kinase inhibitors

Background

T790M mutation is a major mechanism for EGFR-TKI failure. However, few studies explored its correlation with failure patterns and response duration partly due to difficulty in re-biopsy. Droplet digital PCR (ddPCR) is able to detect the frequency and abundance of T790M non-invasively in circulating tumor DNA (ctDNA).

Methods

314 patients with advanced or recurrent NSCLC who had progressed during EGFR-TKIs treatment were enrolled prospectively (NCT02418234). Blood samples were drawn within two weeks from PD occurred. T790M mutations were both evaluated by ARMS and ddPCR. EGFR-TKIs failures were divided into three patterns, chest limited (CF, PD due to lesions limited in chest), brain limited (BF, PD due to lesions limited in intracranial), and other sites failures (OF, PD due to lesions in other distant site or multiple sites including chest or intracranial). The frequency and abundance of T790M mutations were analyzed for association with failure patterns and disease characteristics.

Results

T790M mutations were detected in 30.9% (97/314) and 46.8% (147/314) patients by ARMS and ddPCR. The median abundance of T790M mutation was 1.2% (0.03% to 70.3%). The overall concordance was 78.3% (246/314) between ARMS and ddPCR, 94.6% (158/167) for ARMS^T790M-/ddPCR^T790M-, and 59.9% for ARMS^T790M+/ddPCR^T790M+. There were 62.4% (196/314), 10.8% (34/314), and 26.8% (84/314) patients in failure patterns of CF, BF, OF, respectively. 25% (49/196), 5.9% (2/34), and 54.8% (46/84) patients with PD patterns of CF, BF, and OF were detected ARMS^T790M+ (p 

Conclusions

Using plasma samples to detect T790M is feasible. Different TKI failure patterns correlated with T790M ctDNA status as well as the mutation abundance.

Clinical trial identification

NCT02418234

Legal entity responsible for the study

Hangzhou First People's Hospital

Funding

Projects of medical and health technology program in Zhejiang province (WKJ-2J-1532)

Disclosure

All authors have declared no conflicts of interest.