Abstract 101P
Background
Immunotherapy has achieved breakthrough progress in non-small-cell lung cancer (NSCLC), with some patients experiencing long-term benefits. However, reliable tools for predicting the risk of disease progression (PD) in these patients are lacking. Circulating tumor DNA minimal residual disease (ctDNA MRD) has demonstrated predictive values in early-stage and locally advanced NSCLC, but its role in advanced NSCLC remains unclear.
Methods
The CR1STAL study (NCT05198154) is a multicenter prospective cohort study utilizing ctDNA MRD to monitor the risk of PD in advanced NSCLC. Patients with stage IIIB-IV NSCLC receiving first-line immunotherapy who had progression-free survival of 1 year were screened. Peripheral blood samples were collected every 2-3 months, synchronized with radiographic efficacy evaluations. The personalized target-capture panels for ctDNA detection were tailored based on individual tumor variants identified through the ultra-depth sequencing of a 1021-gene panel. A plasma sample with at least one detected variant was defined as ctDNA MRD positive.
Results
30 NSCLC patients were included, with a median age of 63.5 years. 86.7% were male with median follow-up time of 30.2 months (95% CI 28.4 to 32.0 months). Patients underwent ctDNA MRD monitoring with a median frequency of 4 assessments (range: 3 to 8). 50% of patients tested positive of ctDNA MRD. Compare with the negative group, the ctDNA MRD positive group exhibited an increased risk of PD (hazard ratio: 20.73, 95% CI 2.67 to 161.08, p=0.004), offering a median lead time of 6.2 months (95% CI 5.4 to 7.8 months) than radiographic progression. Furthermore, among the 13 patients who experienced PD, 12 were detected as ctDNA MRD positive, demonstrating a sensitivity of 92.3% and a positive predictive value of 80%. Among the 17 patients with non-PD, 14 were confirmed as ctDNA MRD negative, exhibiting a specificity of 82.4% and negative predictive value of 93.3%.
Conclusions
ctDNA MRD emerges a promising biomarker to predict the risk of PD in advanced NSCLC patients with long-term response to immunotherapy. The surveillance of ctDNA MRD enables earlier detection of PD and facilitates prompt intervention in high-risk patients.
Clinical trial identification
NCT05198154: ctDNA Analysis to Monitor the Risk of Progression after First-line lmmunotherapy in Patients with Advanced NSCLC (CR1STAL).
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
83P - Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in eary high risk breast cancer: The CITUCEL trial update
Presenter: Roberto Borea
Session: Poster session 07
84P - Advancing precision oncology: Integrating immune landscape and genomics for tailored therapy in metastatic cancer patients
Presenter: Eurydice Angeli
Session: Poster session 07
85P - True single-circulating tumor cell genomics reveals enriched therapy-resistance signatures in advanced colorectal cancer patients
Presenter: Manoj Dongare
Session: Poster session 07
Resources:
Abstract
86P - Making the precision oncology landscape of Europe and the Republic of Ireland programmatically accessible
Presenter: Brendan Reardon
Session: Poster session 07
87P - Application of tissue and liquid-based next generation sequencing (NGS) for comprehensive genomic profiling: Evaluating the clinical value of ctDNA technology in treatment decision making
Presenter: Fatima Usman
Session: Poster session 07
88P - Next-generation sequencing (NGS) in routine care: Medical practice in 24 countries from the pan-cancer WAYFIND-R registry
Presenter: Christophe Le Tourneau
Session: Poster session 07
89P - Comprehensive genomic profiling of circulating tumor DNA for treatment recommendation: A sub-project of the IMPRESS-Norway trial
Presenter: Ingrid Dyvik
Session: Poster session 07
90P - Clonal haematopoiesis of indeterminate potential (CHIP) might mislead interpretation of ATM and CHEK2 alterations detected on liquid biopsies
Presenter: Pasquale Rescigno
Session: Poster session 07
91P - Ultra-sensitive ctDNA NGS assay enhances genomic profiling for advanced HR-positive, HER2-negative breast cancer on endocrine therapy
Presenter: Hao Liao
Session: Poster session 07
92P - Transformative diagnostics in urothelial carcinoma: Utilizing targeted NGS and LP-WGS for non-invasive detection and personalized medicine
Presenter: Huan Zhao
Session: Poster session 07