O2-10-4A PROSPECTIVE OBSERVATIONAL STUDY FOR MONITORING EGFR T790M USING PLASMA DNA IN LUNG CANCER PATIENTS

Abstract Background: Detection of mutations with plasma DNA isolated from peripheral blood is an alternative method of biopsy. A novel sensitive, fully-automated monitoring system, MBP-QP, was established in our laboratory to detect T790M, a gatekeeper mutation of EGFR, using plasma DNA. To determine the usefulness of the MBP-QP method for monitoring T790M during treatment with EGFR-TKI, a prospective clinical study was performed. 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. 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 concordance rate was 63%. Conclusion: 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 patients with PD. The relationship between T790M positivity and detailed characteristics of progression will be presented.