106P - Longitudinal molecular characterization in plasma of EGFR mutant non-small cell lung cancer (NSCLC) experiencing early progression (EPD) on first-line osimertinib (Osi)

Background

REM trial is an ongoing translational, prospective multicentre study exploring the role of plasma and tissue genotyping in EGFR-mutated advanced (a) NSCLC patients (pts) during treatment with Osi according to clinical practice. We present preliminary results concerning molecular characterization in plasma focusing on pts experiencing early progression on first-line Osi.

Methods

Pts with EGFR-mutated aNSCLC are prospectively enrolled. Liquid biopsy is performed at the time of Osi start (T0), after 10 (T1) and 28 days (T2), and upon radiological or clinical progression (PD) (T3). Plasmatic EGFR mutations are tested at each timepoint using real-time polymerase chain reaction (RT-PCR). Clearance at specific timepoints is defined as the absence of detectable plasmatic EGFR mutant cfDNA. Next-generation sequencing (NGS) with 77-gene panel is performed at T0 and T3. EPD was defined as PD within 9 months (m) since the start of Osi.

Results

We present preliminary analyses on the first 74 enrolled pts. After a median follow-up of 7.4 m (95%CI 9.0-13.0), objective response rate was 66% (95%CI 53%-77%) and 13 pts (17%) experienced EPD. No clinical feature was associated with the risk of EPD. Clearance of cfDNA was observed at T1 in 37 pts (56%) and at T2 in 48 pts (77%). Lack of clearance at T1 and T2 was associated with higher probability of experiencing EPD (p=0.04, p=0.02), while baseline EGFR positivity in plasma was not. Results of T0 NGS was available for 49 pts (64%). The most prevalent co-mutations (mut) identified were TP53 (N=19, 38%) and PIK3CA (N=7, 14%) mut. Baseline TP53 co-mut significantly increased the risk for EPD (p=0.002). Pts with a basal p53 co-mut experienced significantly worse progression-free survival (HR 3.82, 95%CI 1.27-11.4, p=0.017) and overall survival (HR 8.69, 95%CI 2.06-36.7, p=0.031).

Conclusions

Our preliminary data confirm feasibility of longitudinal characterization in plasma in clinical practice. Clearance of EGFR mut after 10 days since Osi start and TP53 co-mut were able to identify pts at risk for EPD. Data warrant validation for use in clinical practice decision making.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Università degli Studi di Padova.

Funding

AstraZeneca.

Disclosure

L. Bonanno: Financial Interests, Institutional, Advisory Board: AstraZeneca, MSD, BMS, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, Boehringer Ingelheim, MSD, BMS, Janssen, PharmaMar, Arcus Biosciences. L. Calvetti: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Roche. A. Pavan: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS. A. Dal Maso: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD. S. Frega: Financial Interests, Personal, Invited Speaker: MSD. G. Pasello: Financial Interests, Personal, Invited Speaker: Amgen, Eli Lilly, Novartis, MSD, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Janssen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, unconditioned support: AstraZeneca, MSD; Non-Financial Interests, Principal Investigator: AstraZeneca, Roche, Novartis, Lilly, Janssen, PharmaMar. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Eli Lilly, Merck serono, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Institutional, Local PI: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.