AI Article Synopsis
- The study examines the use of plasma circulating tumor DNA (ctDNA) analysis to predict outcomes in patients with advanced non-small cell lung cancer (NSCLC) that have specific EGFR mutations.* -
- Data was collected from two phase III trials (AURA3 and FLAURA), focusing on patients treated with either osimertinib or other therapies, showing that non-detectable plasma EGFR mutations correlate with longer progression-free survival (mPFS).* -
- Findings suggest that monitoring ctDNA changes as early as three weeks into treatment can help predict patient outcomes in advanced NSCLC, highlighting its potential as a useful tool in personalized medicine.*
Article Abstract
Purpose: Plasma circulating tumor DNA (ctDNA) analysis is used for genotyping advanced non-small cell lung cancer (NSCLC); monitoring dynamic ctDNA changes may be used to predict outcomes.
Patients And Methods: This was a retrospective, exploratory analysis of two phase III trials [AURA3 (NCT02151981), FLAURA (NCT02296125)]. All patients had EGFR mutation-positive (EGFRm; ex19del or L858R) advanced NSCLC; AURA3 also included T790M-positive NSCLC. Osimertinib (FLAURA, AURA3), or comparator EGFR-tyrosine kinase inhibitor (EGFR-TKI; gefitinib/erlotinib; FLAURA), or platinum-based doublet chemotherapy (AURA3) was given. Plasma EGFRm was analyzed at baseline and Weeks 3/6 by droplet digital PCR. Outcomes were assessed by detectable/non-detectable baseline plasma EGFRm and plasma EGFRm clearance (non-detection) at Weeks 3/6.
Results: In AURA3 (n = 291), non-detectable versus detectable baseline plasma EGFRm had longer median progression-free survival [mPFS; HR, 0.48; 95% confidence interval (CI), 0.33-0.68; P < 0.0001]. In patients with Week 3 clearance versus non-clearance (n = 184), respectively, mPFS (months; 95% CI) was 10.9 (8.3-12.6) versus 5.7 (4.1-9.7) with osimertinib and 6.2 (4.0-9.7) versus 4.2 (4.0-5.1) with platinum-pemetrexed. In FLAURA (n = 499), mPFS was longer with non-detectable versus detectable baseline plasma EGFRm (HR, 0.54; 95% CI, 0.41-0.70; P < 0.0001). For Week 3 clearance versus non-clearance (n = 334), respectively, mPFS was 19.8 (15.1 to not calculable) versus 11.3 (9.5-16.5) with osimertinib and 10.8 (9.7-11.1) versus 7.0 (5.6-8.3) with comparator EGFR-TKI. Similar outcomes were observed by Week 6 clearance/non-clearance.
Conclusions: Plasma EGFRm analysis as early as 3 weeks on-treatment has the potential to predict outcomes in EGFRm advanced NSCLC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/1078-0432.CCR-22-3146 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma EGFR mutation ctDNA dynamics in patients with advanced EGFR-mutated NSCLC treated with Icotinib: phase 2 multicenter trial result.
Sci Rep
October 2024
Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Fuma Road, Jin'an District, 350014, Fuzhou, China.
Plasma epidermal growth factor receptor mutation (EGFRm) circulating tumor DNA (ctDNA) dynamics exhibit promise in predicting outcomes in patients with EGFRm-advanced non-small cell lung cancer (NSCLC). However, there remains limited trial-level data on integrating ctDNA monitoring into clinical practice. We performed a prospective, multicenter trial to investigate the relationship between EGFRm ctDNA dynamic changes and clinical outcomes in NSCLC patients with EGFRm.
View Article and Find Full Text PDFOsimertinib-induced DNA resistance mutations in cerebrospinal fluid of epidermal growth factor receptor-mutated non-small-cell lung carcinoma patients developing leptomeningeal metastases: Osimertinib Resistance Analysis-leptomeningeal metastases study.
Neuro Oncol
December 2024
Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Article Synopsis
- The study investigates the challenges of diagnosing and treating leptomeningeal metastases (LM) in patients with EGFR mutation positive non-small cell lung cancer (NSCLC) who are being treated with osimertinib, focusing on identifying resistance mechanisms in cerebrospinal fluid (CSF) and plasma.
- A group of 28 patients was analyzed, with a high detection rate of the driver mutation in CSF, but resistance mechanisms were found in 27%, indicating limitations in treatment options available at this time.
- After four weeks on an escalated osimertinib dosage, many patients showed stabilization or worsening of symptoms, suggesting that while some had radiological improvement, overall clinical efficacy remains
Detecting Small Cell Transformation in Patients with Advanced EGFR Mutant Lung Adenocarcinoma through Epigenomic cfDNA Profiling.
Clin Cancer Res
September 2024
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Purpose: Histologic transformation to small cell lung cancer (SCLC) is a mechanism of treatment resistance in patients with advanced oncogene-driven lung adenocarcinoma (LUAD) that currently requires histologic review for diagnosis. Herein, we sought to develop an epigenomic cell-free DNA (cfDNA)-based approach to noninvasively detect small cell transformation in patients with EGFR mutant (EGFRm) LUAD.
Experimental Design: To characterize the epigenomic landscape of transformed (t)SCLC relative to LUAD and de novo SCLC, we performed chromatin immunoprecipitation sequencing (ChIP-seq) to profile the histone modifications H3K27ac, H3K4me3, and H3K27me3; methylated DNA immunoprecipitation sequencing (MeDIP-seq); assay for transposase-accessible chromatin sequencing; and RNA sequencing on 26 lung cancer patient-derived xenograft (PDX) tumors.
Overcoming Osimertinib Resistance with AKT Inhibition in EGFRm-Driven Non-Small Cell Lung Cancer with PIK3CA/PTEN Alterations.
Clin Cancer Res
September 2024
Bioscience, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
Article Synopsis
- Osimertinib is a targeted therapy for lung adenocarcinoma driven by EGFR mutations, significantly enhancing progression-free survival for patients, though many eventually show disease progression.
- * An analysis of genetic changes in blood samples from patients undergoing osimertinib treatment revealed frequent PIK3CA/AKT/PTEN mutations, which contribute to resistance against the drug.
- * Combining osimertinib with the AKT inhibitor capivasertib demonstrates improved effectiveness in overcoming resistance caused by these genetic alterations, offering a new treatment strategy for affected patients.*
Osimertinib Plasma Trough Concentration in Relation to Brain Metastases Development in Patients With Advanced -Mutated NSCLC.
JTO Clin Res Rep
April 2024
Department of Pulmonary Diseases, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Introduction: Brain metastases (BM) are common in patients with advanced -mutated (m+) NSCLC. Despite good BM-related outcomes of osimertinib, several patients still experience intracranial progression. A possible explanation is pharmacologic failure due to low plasma trough levels (C) and consequently limited intracranial osimertinib exposure.
View Article and Find Full Text PDFWant 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!