T790M mutation detection in circulating tumor DNA (ctDNA) has shown great potential in clinical application. However, few studies reported the influence of plasma T790M mutation on selection of clinical treatment and survival time after first generation TKI resistance.
307 patients with advanced or recurrent NSCLC who had progressed during EGFR-TKIs treatment were enrolled prospectively (NCT02418234) from March 2015 to March 2016. Blood samples were drawn within two weeks from PD occurred. T790M mutations were evaluated by droplet digital PCR. We undertook follow-up every 3 months by phone till April 2017. The median follow-up time was 11 months (range, 2 to 22 months).
Our results showed that the median survival time after TKI progression was 17.5 months (95%CI, 15-20 months) and six kinds of treatments were used in these patients, including continuation of TKI (27.0%), AZD9291 (27.7%), chemotherapy with or without radiotherapy (15.3%), TKI combined with chemo/RT (6.5%), switch to another TKI (2.6%) and best supportive care (11.4%). 88.6% of patients received subsequent treatment. T790M- patients were likely to receive continuation of original TKIs, which accords for 29.5% (52/176), the percentage of switch to another TKI is the lowest (2.8%, 5/176). In T790M+ patients, AZD9291 is the first choice as the subsequent treatment, which accords for 38.9% (51/131). Switch to another TKI (2.2%, 3/131) and TKI combined with chemo/RT (6.1%, 8/131) is the least selection. Although most T790M- patients received continuation of original TKIs, combination of TKI and chemotherapy/radiotherapy seems to be a better choice, which got the longest survival than other treatment. For T790M+ patients, patients who choose AZD9291 had the longest survival.
T790M status in ctDNA have the great influence on clinical decision of the subsequent treatment, AZD9291 is the most frequent choice for the plasma T790M+ patients, which contributed the longest survival after 1st generation EGFR-TKI resistance.
Clinical trial identification
Legal entity responsible for the study
Projects of Medical and Health Technology in Zhejiang Province (WKJ-2J-1532)
All authors have declared no conflicts of interest.