Abstract 225P
Background
Circulating tumor DNA (ctDNA) is an emerging biomarker for monitoring tumor burden, detecting minimal residual disease, and predicting outcomes in patients (pts) with non-small cell lung cancer (NSCLC). This prospective, single-center study evaluates the prognostic value of ctDNA levels measured before and after concurrent chemoradiotherapy (cCRT) in pts with unresectable stage III NSCLC.
Methods
This study included pts with stage III NSCLC treated with cCRT, with or without durvalumab consolidation as per local practice guidelines. ctDNA dynamics were analyzed using Guardant Reveal®, a tissue-free epigenomic assay intended for detection and quantification of ctDNA. Pre- and post-cCRT ctDNA levels were assessed, and association with progression-free survival (PFS) and overall survival (OS) was evaluated.
Results
This study included 62 pts, predominantly male (82%), adenocarcinoma (40%) and stage IIIA (42%) NSCLC. Durvalumab consolidation was administered in 40% of pts. Pre-cCRT ctDNA was detected in 90% of pts (56/62).With a median follow-up of 18.4 months (m), 50% of pre-cCRT ctDNA-positive pts had died compared to 0% of ctDNA-negative. Post-cCRT ctDNA was assessed in 46 pts, with positivity in 21.7%. This was associated with shorter median PFS (6.8 m vs. not reached [NR], p=0.00002) and OS (19.8 mvs. NR, p=0.004), compared to ctDNA-negative pts. Post-cCRT ctDNA-negative pts that received durvalumab had the best mPFS (NR), followed by ctDNA-negative pts not treated with durvalumab (21 m, p=0.0031) and ctDNA-positive pts treated with durvalumab (20.6 m, p=0.0263), with the worst mPFS for ctDNA-positive pts not treated with durvalumab (6.5 m, p < 0.0001). When looking at the dynamics between pre- and post-cCRT ctDNA detection, median PFS values were: ctDNA (−/−) NR, (+/−) NR, (+/+) 6.9 m, and (−/+) 4.4 m.
Conclusions
Patients with unresectable stage III NSCLC who were ctDNA-negative at baseline and after undergoing cCRT had improved PFS and OS compared to ctDNA-positive pts. Durvalumab consolidation treatment improved outcomes for both post-cCRT ctDNA-positive and -negative pts. This study underscores the clinical utility of ctDNA as a biomarker for monitoring disease status, guiding treatment strategies and improving patient outcomes.
Legal entity responsible for the study
The authors.
Funding
Guardant Health.
Disclosure
N. Navarro-Gorro: Financial Interests, Personal, Invited Speaker: KiowaKirin, AstraZeneca, MSD, Merck; Financial Interests, Personal, Other, Travel grant: Johnson & Johnson. L. Masfarre Pinto: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim. P.F. Simoes Da Rocha: Other, Personal, Other, Congress and travel: MSD, BMS, AstraZeneca, Kyowa Kirin, Roche. A. Taus Garcia: Financial Interests, Personal, Invited Speaker: GSK, GSK, Takeda, Roche, AstraZeneca, Pfizer, Eisai; Financial Interests, Personal, Advisory Board: Sanofi, BMS, AstraZeneca. S. Clave: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Roche, Takeda, Novartis; Financial Interests, Personal, Advisory Board: Lilly. B. Bellosillo Paricio: Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Merck Serono, Roche, Thermofisher, Pfizer, BMS; Financial Interests, Personal, Expert Testimony: Janssen; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche. J. Hayes, I. Roca Carreras, F.N. Riva: Financial Interests, Personal and Institutional, Full or part-time Employment: Guardant Health; Financial Interests, Personal and Institutional, Stocks/Shares: Guardant Health. E. Arriola Aperribay: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, AstraZeneca, Boehringer Ingelheim, Lilly, Takeda; Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal, Research Grant: Pfizer. All other authors have declared no conflicts of interest.