1236P - ctDNA-Lung-Detect: Profiling of non-shedding ctDNA early stage resected non-small cell lung cancers

Background

ctDNA-Lung-Detect is a multi-centre investigator-initiated prospective study assessing circulating tumour DNA (ctDNA) detection and association with recurrence free survival in patients with early stage, resected non-small cell lung cancer (NSCLC) (NCT05254782). Herein, we describe a sub-population of non-shedding ctDNA tumours, to help identify patients who remain high risk of relapse and those who may benefit from treatment escalation.

Methods

Patients with clinical stage I (T1-2N0) or multifocal T3-4 <4cm N0 NSCLC planned for resection consented to plasma ctDNA assessment before and after surgery, and at 12 months post-resection or relapse using the tumour-informed RaDaR® assay.

Results

Between July 2021 and April 2024, 231 patients were enrolled; 138 patients have preoperative ctDNA results. In 76.1% (105/138), ctDNA was not detected pre-operatively. Non-shedding patients were less likely to be male vs female (OR 0.40; CI 95% 0.18, 0.89, p <0.05); Current smokers vs never smokers (OR 0.21; 0.06, 0.74, p <0.01); Tumours were less likely to have non-squamous histology (OR 0.08; 0.02, 0.26, p <0.0001); Less likely to be T3/4 vs T1 (OR 0.04; 0.01, 0.16, p <0.0001) and less likely to be node positive vs negative (OR 0.22; 0.07, 0.71, p <0.01). An identifiable driver mutation (EGFR, ALK, KRAS G12C, ROS1, RET, MET exon 14 skipping, BRAF V600E or ERBB2) was more likely to be present when ctDNA was not detected (OR 2.71; 1.11, 6.59, p <0.03) and tumours were less likely to be PD-L1 >50% compared to <1% (OR 0.22; 0.08, 0.65, p <0.006). Four patients recurred where ctDNA was not detected; all were female with adenocarcinomas; one was a never smoker, two were previous smokers and one was a current smoker; three were stage 1, one was stage 2, and all had driver mutations.

Conclusions

This study represents one of the largest prospective cohorts of ctDNA assessment in patients with early stage resected NSCLC. Non-shedding patients were less likely to be male, current smokers, have PD-L1 high tumours, and were more likely to have an identifiable driver mutation. As data matures, we will be able to characterize non-shedding patients whom are at high risk of relapse and offer personalized approaches to escalation of treatment.

Clinical trial identification

NCT05254782.

Editorial acknowledgement

Legal entity responsible for the study

University Health Network.

Funding

Ontario Institute for Cancer Research, Princess Margaret Cancer Foundation Grand Challenge, Neogenomics (RADAR assay).

Disclosure

C. Pipinikas, A. Chevalier: Financial Interests, Personal and Institutional, Financially compensated role: Neogenomics. All other authors have declared no conflicts of interest.