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Liquid Biopsy and 18F-FDG PET/CT Derived Parameters as Predictive Factors of Osimertinib Treatment in Advanced
Alessandro Leonetti1, Veronica Cervati2, Roberta Minari1
1Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Objectives:
Despite the outstanding results achieved by osimertinib for the treatment of advanced EGFR-mutated NSCLC, the development of resistance is almost inevitable. While molecular mechanism responsible for osimertinib resistance are being mostly revealed, the definition of predictive biomarkers is crucial in order to identify patients at higher risk of progression and optimize treatment strategy.
Materials And Methods:
This is a prospective single-center study aimed to assess the potential role of liquid biopsy and 18F-FDG PET/CT derived metabolic parameters as noninvasive predictive biomarkers of osimertinib outcomes in advanced EGFR-mutated NSCLC patients. Patients underwent blood samples for ctDNA analysis at baseline, after 15 days and 1 month (t1) of osimertinib. 18F-FDG PET/CT was performed at baseline and after 1 month of osimertinib.
Results:
Seventy-two advanced EGFR-mutated NSCLC patients treated with osimertinib in first (n = 63) and in second-line (n = 9) were prospectively enrolled. Baseline positive shedding status was significantly associated with a shorter progression-free survival (PFS) (9.5 vs. 29.2 months, P = .031). Early metabolic response (MR) led to improved PFS (16.8 vs. 5.5 months, P = .038) and OS (35.2 vs. 15.3 months, P = .047). Early MR was significantly correlated with subsequent radiologic response (P = .010). All 18F-FDG PET/CT baseline parameters were significantly related to baseline EGFR activating mutation allele frequency. Both clearance and no detection of EGFR at t1 were significantly associated with MR (P = .001 and P = .004, respectively).
Conclusion:
Molecular and 18F-FDG PET/CT derived metabolic parameters might represent a useful tool to predict osimertinib outcome in advanced EGFR-mutated NSCLC patients.
Insights
Liquid biopsy and 18F-FDG PET/CT metabolic parameters can predict osimertinib treatment outcomes in advanced EGFR-mutated NSCLC. Early detection of EGFR mutations and metabolic response are key indicators for improved progression-free survival and overall survival.
Area of Science:
- Oncology
- Molecular Biology
- Radiology
Background:
- Osimertinib is effective for advanced EGFR-mutated NSCLC, but resistance is common.
- Identifying predictive biomarkers is crucial for optimizing treatment strategies and managing resistance.
Purpose of the Study:
- To assess liquid biopsy and 18F-FDG PET/CT metabolic parameters as noninvasive biomarkers for predicting osimertinib outcomes.
- To identify patients at higher risk of progression and optimize treatment.
Main Methods:
- Prospective single-center study of 72 advanced EGFR-mutated NSCLC patients treated with osimertinib.
- ctDNA analysis via liquid biopsy at baseline, 15 days, and 1 month.
- 18F-FDG PET/CT scans at baseline and 1 month.
Main Results:
- Baseline ctDNA shedding was linked to shorter progression-free survival (PFS).
- Early metabolic response (MR) on PET/CT correlated with improved PFS and overall survival (OS).
- EGFR mutation allele frequency related to baseline PET/CT parameters; ctDNA clearance at 1 month associated with MR.
Conclusions:
- Molecular and metabolic parameters from liquid biopsy and 18F-FDG PET/CT show promise in predicting osimertinib outcomes.
- These noninvasive biomarkers can aid in patient stratification and treatment planning for EGFR-mutated NSCLC.
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