Identifying advanced stage NSCLC patients who benefit from afatinib therapy using 18F-afatinib PET/CT imaging
Eveline A van de Stadt1, Maqsood Yaqub2, Adriaan A Lammertsma2
1Department of Pulmonology, Amsterdam UMC location VUmc, Amsterdam, the Netherlands.
Objectives:
Non-small cell lung cancer (NSCLC) tumors harboring common (exon19del, L858R) and uncommon (e.g. G719X, L861Q) activating epidermal growth factor receptor (EGFR) mutations are best treated with EGFR tyrosine kinase inhibitors (TKI) such as the first-generation EGFR TKI erlotinib, second-generation afatinib or third-generation osimertinib. However, identifying these patients through biopsy is not always possible. Therefore, our aim was to evaluate whether 18F-afatinib PET/CT could identify patients with common and uncommon EGFR mutations. Furthermore, we evaluated the relation between tumor 18F-afatinib uptake and response to afatinib therapy.
Materials And Methods:
18F-afatinib PET/CT was performed in 12 patients: 6 EGFR wild type (WT), 3 EGFR common and 3 EGFR uncommon mutations. Tumor uptake of 18F-afatinib was quantified using TBR_WB60-90 (tumor-to-whole blood activity ratio 60-90 min post-injection) for each tumor. Response was quantified per lesion using percentage of change (PC): [(response measurement (RM)-baseline measurement (BM))/BM]×100. Statistical analyses were performed using t-tests, correlation plots and sensitivity/specificity analysis.
Results:
Twenty-one tumors were identified. Injected dose was 348 ± 31 MBq. Group differences were significant between WT versus EGFR (common and uncommon) activating mutations (p = 0.03). There was no significant difference between EGFR common versus uncommon mutations (p = 0.94). A TBR_WB60-90 cut-off value of 6 showed the best relationship with response with a sensitivity of 70 %, a specificity of 100 % and a positive predictive value of 100 %.
Conclusion:
18F-afatinib uptake was higher in tumors with EGFR mutations (common and uncommon) compared to WT. Furthermore, a TBR_WB60-90 cut-off of 6 was found to best predict response to therapy. 18F-afatinib PET/CT could provide a means to identify EGFR mutation positive patients who benefit from afatinib therapy.
Insights
18F-afatinib PET/CT can identify non-small cell lung cancer patients with common and uncommon EGFR mutations. This imaging technique also predicts response to afatinib therapy, aiding treatment decisions.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Non-small cell lung cancer (NSCLC) treatment relies on identifying epidermal growth factor receptor (EGFR) mutations.
- EGFR tyrosine kinase inhibitors (TKIs) like afatinib are effective, but biopsy for mutation status is not always feasible.
- Novel imaging methods are needed to non-invasively detect EGFR mutations and predict treatment response.
Purpose of the Study:
- To evaluate 18F-afatinib PET/CT for identifying NSCLC patients with common and uncommon EGFR mutations.
- To assess the correlation between tumor 18F-afatinib uptake and response to afatinib therapy.
Main Methods:
- 18F-afatinib PET/CT was performed on 12 patients with NSCLC (6 EGFR wild type, 3 common EGFR mutations, 3 uncommon EGFR mutations).
- Tumor uptake was quantified using tumor-to-whole blood activity ratio (TBR_WB60-90).
- Lesion response was measured by percentage of change (PC) and statistically analyzed.
Main Results:
- 18F-afatinib uptake was significantly higher in tumors with EGFR mutations (common and uncommon) compared to wild-type tumors (p=0.03).
- No significant difference in uptake was observed between common and uncommon EGFR mutations (p=0.94).
- A TBR_WB60-90 cut-off of 6 demonstrated high accuracy (70% sensitivity, 100% specificity) in predicting response to afatinib therapy.
Conclusions:
- 18F-afatinib PET/CT can differentiate EGFR-mutated NSCLC from wild-type tumors.
- The imaging biomarker predicts response to afatinib, potentially guiding treatment selection.
- 18F-afatinib PET/CT offers a non-invasive method to identify patients likely to benefit from afatinib therapy.
