Monitoring Egfr T790M Using Plasma Dna in Lung Cancer Patients Treated with Egfr Tyrosine Kinase Inhibitor in a Prospective Observational Study

Abstract

ABSTRACT Aim: Use of plasma DNA to detect mutations has spread widely as a form of liquid biopsy. The gatekeeper T790M mutation of EGFR has been observed in half of lung cancer patients who acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI). We recently developed a novel sensitive, fully-automated monitoring system, MBP-QP(mutaton-based PCR and quenching probe), to detect T790M using plasma DNA. This study was performed to determine the usefulness of the MBP-QP method for monitoring T790M during treatment with EGFR-TKI. Methods: This was a prospective, multicenter, observational study involving lung adenocarcinoma patients carrying EGFR activating mutations, such as L858R and exon 19 deletions, who were treated with EGFR-TKI. The primary objective was to determine whether T790M could be detected using plasma DNA at the time of progressive disease (PD). The secondary objective was to assess correspondence between T790M measured using plasma and that using cancer specimens. The association between detection of T790M and effect of EGFR-TKI was also investigated as an exploratory objective. Results: Ninety non-small cell lung cancer patients treated with EGFR-TKI were enrolled from seven hospitals in Japan: 92.1% had adenocarcinoma, 62% at stage IV, and 29% had postoperative recurrent disease. According to the investigators' evaluations, T790M was detected in 26% (15/58) of the patients who acquired resistance to EGFR-TKI. A central review showed that the frequency of T790M positives among the patients with PD was 22% (12/55). When EGFR-TKI was discontinued because of PD, T790M was detected in 33% (17/52), whereas any patients who were discontinued for other reasons such as adverse effects did not show T790M positivity. Eight re-biopsy specimens were obtained at the time of occurrence of PD, and the concordane rate was 63%. The frequncy of T790M positive was higher when metastatic lesions were spread compared to enlargement of primary lesions. The cases with T790M positive have been analyzing in detail. Conclusions: T790M was detected in plasma DNA at the time of PD occurrence. Compared to the frequency using re-biopsy reported by other papers, liquid biopsy covered approximately half of the total patiets with PD. The relationship between T790M positivity and detailed characteristics of progression was analyzed. Disclosure: Y. Urata: other substantive relationships(myself):AstraZeneca, Chugai pharmaceutical; M. Satouchi: other substantive relationships(myself):AstraZeneca, Chugai pharmaceutical; K. Aoe: corporate-sponsored research:Elli Lilly(myself). All other authors have declared no conflicts of interest.