Purpose: As immune checkpoint inhibitors (ICI) become increasingly used in frontline settings, identifying early indicators of response is needed. Recent studies suggest a role for circulating tumor DNA (ctDNA) in monitoring response to ICI, but uncertainty exists in the generalizability of these studies. Here, the role of ctDNA for monitoring response to ICI is assessed through a standardized approach by assessing clinical trial data from five independent studies.
Patients And Methods: Patient-level clinical and ctDNA data were pooled and harmonized from 200 patients across five independent clinical trials investigating the treatment of patients with non-small-cell lung cancer with programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1)-directed monotherapy or in combination with chemotherapy. CtDNA levels were measured using different ctDNA assays across the studies. Maximum variant allele frequencies were calculated using all somatic tumor-derived variants in each unique patient sample to correlate ctDNA changes with overall survival (OS) and progression-free survival (PFS).
Results: We observed strong associations between reductions in ctDNA levels from on-treatment liquid biopsies with improved OS (OS; hazard ratio, 2.28; 95% CI, 1.62 to 3.20; < .001) and PFS (PFS; hazard ratio 1.76; 95% CI, 1.31 to 2.36; < .001). Changes in the maximum variant allele frequencies ctDNA values showed strong association across different outcomes.
Conclusion: In this pooled analysis of five independent clinical trials, consistent and robust associations between reductions in ctDNA and outcomes were found across multiple end points assessed in patients with non-small-cell lung cancer treated with an ICI. Additional tumor types, stages, and drug classes should be included in future analyses to further validate this. CtDNA may serve as an important tool in clinical development and an early indicator of treatment benefit.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384957 | PMC |
| http://dx.doi.org/10.1200/PO.21.00372 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
IQGAP3 activates Hedgehog signaling to confer stemness and metastasis via up-regulating GLI1 in lung cancer.
Sci Rep
December 2024
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Lung cancer ranks as the most prevalent malignant neoplasm worldwide, contributing significantly to cancer-related mortality. Stemness is a well-recognized factor underlying radiotherapy resistance, recurrence and metastasis in non-small-cell lung cancer (NSCLC) patients. Our prior investigations have established the role of IQ motif containing GTPase-activating protein 3 (IQGAP3) in mediating radiotherapy resistance in lung cancer, but its impact on lung cancer stemness remains unexplored.
View Article and Find Full Text PDFKRAS inhibitors: resistance drivers and combinatorial strategies.
Trends Cancer
December 2024
Charité - Universitätsmedizin Berlin, Institute of Pathology, Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, German Cancer Research Center (DKFZ), Heidelberg, Germany; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
In 1982, the RAS genes HRAS and KRAS were discovered as the first human cancer genes, with KRAS later identified as one of the most frequently mutated oncogenes. Yet, it took nearly 40 years to develop clinically effective inhibitors for RAS-mutant cancers. The discovery in 2013 by Shokat and colleagues of a druggable pocket in KRAS paved the way to FDA approval of the first covalently binding KRAS inhibitors, sotorasib and adagrasib, in 2021 and 2022, respectively.
View Article and Find Full Text PDFEmergence of Circulating Tumor DNA as a Precision Biomarker in Lung Cancer Radiation Oncology and Beyond.
Hematol Oncol Clin North Am
December 2024
Department of Radiation Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address:
Circulating tumor DNA (ctDNA) is emerging as a transformative biomarker in the management of non-small cell lung cancer (NSCLC). This review focuses on its role in detecting minimal residual disease (MRD), predicting treatment response, and guiding therapeutic decision-making in radiation oncology and immunotherapy. Key studies demonstrate ctDNA's prognostic value, particularly in identifying relapse risk and refining patient stratification for curative-intent and consolidative treatments.
View Article and Find Full Text PDFNeoadjuvant and adjuvant osimertinib in stage IA-IIIA, EGFR-mutant non-small cell lung cancer (NORA).
J Thorac Oncol
December 2024
Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
Introduction: Treatment with adjuvant osimertinib for three years is the standard-of-care for resected stage IB-IIIA non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-mutations. The role of neoadjuvant osimertinib in the perioperative setting is yet to be elucidated in the NeoADAURA study (NCT04351555).
Methods: This is a single center, pilot study of patients with clinical stage IA-IIIA NSCLC (AJCC 8th edition) harboring an activating EGFR mutation (Exon 19 deletion, L858R) (NCT04816838).
Immunotherapy or targeted therapy with or without stereotactic radiosurgery for patients with brain metastases from melanoma or non-small cell lung cancer - The ETOP 19-21 USZ-STRIKE study.
Lung Cancer
December 2024
Coordinating Center, ETOP IBCSG Partners Foundation, Bern, Switzerland.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!