1331P - Resistance mechanisms in EGFR-mutated advanced non-small cell lung cancer (aNSCLC) patients (pts) treated with first-line osimertinib (osi) and monitoring plasma mutational load: Preliminary results of REM study

Background

The ongoing REM trial is a translational prospective multicenter Italian study aiming to monitor EGFR-mutated pts through liquid biopsy and explore potential mechanisms of primary and acquired resistance.

Methods

EGFR-mutated aNSCLC pts receiving first-line osi are prospectively enrolled. Plasma samples are collected before starting treatment (T0), after 10 (T1) and 28 days (T2) and at the time of radiological/clinical progression (T3). EGFR mutations (mut) in plasma are analyzed by real-time polymerase chain reaction (RT-PCR) and by next-generation sequencing (NGS). A semiquantitative index (SQI) is given by the RT-PCR, related to the amount of EGFR mut cell-free DNA (cfDNA) present in plasma sample. Change from baseline in EGFR SQI is considered as a difference from baseline to different time-points (T0–T1 and T0–T2).

Results

Since August 2022, 34 pts were included (data cut-off March 2023): mainly females (N=24, 70.6%) and never smokers (N=23, 67.6%); median age at diagnosis was 70.5 years (IQR 67-77). The majority of pts had a commonEGFR mut (exon 19 deletion: N=18, 52.9%; L858R mut N=12, 35.3%). The objective response rate was 70.6% (95% CI, 52.5-84.9), while survival data were immature at time of analysis. The concordance between tissue and plasma was 76.5% (95% CI, 58.9-89.3). A higher tumour burden (defined as 3 or more metastatic sites at diagnosis) was related to higher SQI at T0 (OR 3.12, 95% CI: 2.70-12.81, p=0.004). Clearance of plasma EGFR mut at T2 was detected in 20 out of 26 pts (76.9%). A correlation between change in EGFR SQI and response rate was found: a decrease of baseline EGFR SQI (T0-T2) >=50% was associated with increased probability of reaching an objective response (OR: 13.5, 95% CI: 1.1- 165.9, p=0.042). Two pts experienced radiological progression at first assessment and both had no clearance at T2.

Conclusions

EGFR mut monitoring 10 days after the start of first-line osi has the potential to be used as predictive marker in order to personalize treatment of EGFR-mutated aNSCLC pts. Updated results including NGS analyses at T0 and correlation of co-mutations in cfDNA with outcome will be presented at the Conference.

Clinical trial identification

CESC IOV 2021-107-PU.

Editorial acknowledgement

Legal entity responsible for the study

Università degli Studi di Padova.

Funding

AstraZeneca.

Disclosure

L. Bonanno: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, BMS, Novartis, Sanofi, MSD; Non-Financial Interests, Personal and Institutional, Coordinating PI: AstraZeneca; Financial Interests, Personal and Institutional, Funding: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, BMS, Novartis, Lilly, MSD; Non-Financial Interests, Personal and Institutional, Local PI: AstraZeneca, Roche, PharmaMar, MSD. S. Frega: Financial Interests, Personal, Invited Speaker: MSD. G. Pasello: Financial Interests, Personal, Invited Speaker: Amgen, Lilly, Novartis, MSD; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Janssen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, unconditioned support: AstraZeneca; Non-Financial Interests, Principal Investigator: AstraZeneca, Roche, Novartis, Lilly, Janssen, PharmaMar. S. Indraccolo: Financial Interests, Personal, Invited Speaker: AstraZeneca. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Amgen, GSK; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Eli Lilly, Sanofi, Merck Serono, Exact Sciences, Eisai, Olema Oncology; Financial Interests, Institutional, Local PI: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK Daiichi Sankyo, Nerviano; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.