Abstract 3912
Background
15–40% of NSCLC patients harbor EGFR sensitizing mutations. Tyrosine kinase inhibitors (TKI) provide significant clinical benefit in this population, yet all patients will develop resistance. Liquid biopsy has been demonstrated to reliably identify somatic tumor associated EGFR mutations. Quantitative assessment of mutated EGFR driven tumors could potentially be used to monitor disease progression and assess therapeutic response.
Methods
129 patients (68 F/61 M) with tissue biopsy-proofed EGFR sensitizing mutation-positive lung adenocarcinoma who were treated with EGFR-TKI and had one before TKI treatment and at least three post TKI treatment/follow-up blood samples were included in the study. 71% (92/129) patients were non-smokers. Plasma samples were tested with the cobas® EGFR Mutation Test v2, and the Semi-Quantitative Index (SQI) values for each mutation were reported by the software for the target mutation. The SQI is able to reflect a trend in the plasma EGFR mutation load. Molecular progression (MP) is defined as two consecutive non-zero SQI values or detection of T790M.
Results
The most common EGFR mutations detected in the tissue were L858R (53%) and Exon 19 deletion (Ex19Del) (40%). One patient had both Ex19Del and T790M mutations. Plasma cfDNA analyses detected EGFR mutations in 74% (95/129) of the baseline samples. 64 of the 95 patients had MP. On average, MP was 42 days prior to clinical progression (CP) based on RECIST1.1. The PPV and NPV of using MP to predict CP were 84% and 68%, respectively. Analysis of the serial plasmas collected from patients who progressed while on 1st line TKI showed reappearance of the original EGFR sensitizing mutations with increasing SQI levels before emergence of a T790M mutation. T790M mutation was detected in 21% (27/129) of the patients on TKI treatment.
Conclusions
This study clearly demonstrated that monitoring EGFR mutation levels or changes in blood could be a meaningful approach to predict clinical progression for lung adenocarcinoma patients treated with EGFR-TKI. It warrants further studies to demonstrate the potential clinical utility of serial blood EGFR testing in NSCLC management.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3409 - Effect and safety of immune checkpoint inhibitors for brain metastases from non-small cell lung cancer
Presenter: Toshihiko Iuchi
Session: Poster Display session 1
Resources:
Abstract
3683 - Impact of Radiotherapy on efficacy of anti-programmed death 1 (PD-1) antibodies in metastatic NSCLC
Presenter: Evangeline Samuel
Session: Poster Display session 1
Resources:
Abstract
3924 - Pembrolizumab frontline monotherapy in patients with NSCLC and high PD-L1 expression: Real World Data from a European Cohort with focus on subgroups of interest
Presenter: Giannis Mountzios
Session: Poster Display session 1
Resources:
Abstract
3970 - Patients with metastatic non-small cell lung cancer and PD-L1 expression in Germany. Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Presenter: Martin Sebastian
Session: Poster Display session 1
Resources:
Abstract
5350 - The efficacy and safety of pembrolizumab as a first-line therapy in PD-L1 50% positive advanced NSCLC (HOPE-001)
Presenter: Motohiro Tamiya
Session: Poster Display session 1
Resources:
Abstract
3832 - Osimertinib in epidermal growth factor receptor (EGFR) T790M advanced non-small cell lung cancer (NSCLC): analysis of patients with central nervous system (CNS) metastases in a real-world study (ASTRIS)
Presenter: Giulio Metro
Session: Poster Display session 1
Resources:
Abstract
4082 - Real-world (RW) treatment patterns and outcomes for second-line (2L) therapy and beyond in patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC receiving a first-line (1L) first- or second-generation (1G/2G) EGFR tyrosine kinase inhibitor (TKI)
Presenter: Riyaz Shah
Session: Poster Display session 1
Resources:
Abstract
2855 - Impact of ramucirumab (RAM) + erlotinib (ERL) on EGFR mutations in circulating tumor DNA – The 1st report of a biomarker study in Japanese patients from RELAY: Global Ph3 study of ERL + RAM or placebo (PL) in 1L metastatic NSCLC with EGFR activating mutations
Presenter: Kazuto Nishio
Session: Poster Display session 1
Resources:
Abstract
2911 - Apatinib combined with EGFR - TKI in treating advanced non-small cell lung cancer with EGFR - TKI resistance
Presenter: Ruifen Tian
Session: Poster Display session 1
Resources:
Abstract
2100 - Updated analysis of a phase I trial of afatinib (Afa) and bevacizumab (Bev) in chemo-naïve patients (pts) with advanced non-small-cell lung cancer (NSCLC) harboring EGFR-mutations: OLCSG1404
Presenter: Takashi Ninomiya
Session: Poster Display session 1
Resources:
Abstract