653P - Baseline and 3 weeks on-treatment plasma EGFR mutation (EGFRm) dynamics in patients with EGFR mutant advanced NSCLC treated with first-line osimertinib: A prospective, multi-center, real-world analysis

Background

According to FLAURA study, persistence of circulating tumor DNA (ctDNA) plasma EGFRm at 3 weeks could predict poor clinical outcomes in patients(pts) with advanced EGFRm NSCLC receiving first line(1L) osimertinib. Here we explore the dynamic changes of plasma ctDNA EGFRm between baseline and 3 weeks after 1L osimertinib monotherapy in real-world setting in China.

Methods

Treatment-naïve pts with EGFRm (Ex19del or L858R) advanced NSCLC were prospectively tested EGFRm status in plasma ctDNA as baseline. These pts who received osimertinib monotherapy as 1L therapy were tested EGFRm status in plasma ctDNA at 3 weeks. The status of plasma ctDNA EGFRm at baseline and 3 weeks after 1L osimertinib monotherapy were analyzed by Super ARMS-PCR. EGFRm persistence was defined as still detected EGFRm in plasma ctDNA at 3 weeks of 1L osimertinib treatment, where it was detected at baseline.

Results

From 13^rd Jan. 2022 to 15^th Mar. 2024, a total of 511 pts had an evaluable baseline plasma result, of who 398(77.9%) had detected baseline plasma EGFRm. After 3 weeks of 1L Osimertinib treatment, 351 pts had qualified ctDNA EGFRm results, EGFRm clearance was observed in 236(67.2%) pts, 115(32.8%) pts are EGFRm persistence. In pts with baseline-detected plasma EGFRm, plasma EGFRm persistence at 3 weeks was similar between EGFR Ex19del (28.3%) and L858R (32.3%). Furthermore, there was no significant difference in patient with TP53 co-mutation (32.7%) or not (32.8%). Plasma EGFRm persistence at 3 weeks are 35.21% in pts with brain metastasis(BM), and 42.75% in pts without BM (p=0.3658). Larger of the sum of diameters (SOM) according to RECIST 1.1 at baseline was significantly associated with persistence of ctDNA EGFRm at 3 weeks in Cox regression analysis (P=0.0039).

Conclusions

The proportion of ctDNA EGFRm persistence at 3 weeks in this real-world analysis is as similar as previously reported. EGFRm subtype and co-mutation may not significantly influence ctDNA EGFRm persistence. Pts with persistence ctDNA EGFRm at 3 weeks suggested higher tumor burden, maybe need more aggressive treatment to further improve clinical outcome.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Beijing Cancer Prevention & Treatment Society.

Disclosure

All authors have declared no conflicts of interest.