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Stereotactic ablative radiotherapy for acquired resistance to EGFR therapy in metastatic non-small cell lung cancer
Rodolfo Chicas-Sett1, Juan Castilla Martinez1, Abrahan Hernández Blanquisett2
1Department of Radiation Oncology, ASCIRES GRUPO BIOMEDICO, Valencia, Spain.
Abstract:
The advent of targeted therapy has transformed the treatment paradigm and survival of patients with metastatic non-small cell lung cancer (NSCLC) with driver mutations. The development of acquired resistances during treatment with tyrosine kinase inhibitors (TKIs) impedes a prolonged survival in many patients. This fact is leading to the use of locally ablative therapies such as stereotactic ablative radiotherapy (SABR) to counter these resistances. SABR is a non-invasive treatment that can be delivered in multiple locations and has already proven effective in oligometastatic disease. Clinical evidence suggests that the combination of SABR with TKIs prolongs progression-free survival (PFS) in metastatic NSCLC patients with mutations in epidermal growth factor receptor (EGFR), with international guidelines recommending their use in unfavorable scenarios such as oligoprogressive disease. In this publication, we have reviewed the available evidence on EGFR-TKIs resistance mechanisms and the combination of SABR with TKI in metastatic NSCLC with EGFR mutations. We also describe the utility and clinical recommendations of this combination in oligometastatic and oligoprogressive disease.
Insights
Combining stereotactic ablative radiotherapy (SABR) with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) improves progression-free survival for metastatic non-small cell lung cancer (NSCLC) patients. This combination is recommended for oligometastatic or oligoprogressive disease.
Area of Science:
- Oncology
- Medical Physics
- Pharmacology
Background:
- Metastatic non-small cell lung cancer (NSCLC) treatment has improved with targeted therapies, but acquired resistance to tyrosine kinase inhibitors (TKIs) limits long-term survival.
- Stereotactic ablative radiotherapy (SABR) is an effective non-invasive ablative therapy for oligometastatic disease, offering a way to overcome treatment resistance.
Purpose of the Study:
- To review mechanisms of resistance to epidermal growth factor receptor (EGFR)-TKIs in metastatic NSCLC.
- To evaluate the combination of SABR with EGFR-TKIs for metastatic NSCLC patients with EGFR mutations.
- To describe clinical utility and recommendations for this combination in oligometastatic and oligoprogressive disease.
Main Methods:
- Literature review of existing evidence on EGFR-TKI resistance mechanisms.
- Analysis of clinical data regarding the combination of SABR and TKIs in metastatic NSCLC.
- Examination of treatment guidelines for oligometastatic and oligoprogressive NSCLC.
Main Results:
- Clinical evidence supports that combining SABR with TKIs prolongs progression-free survival (PFS) in metastatic NSCLC patients with EGFR mutations.
- International guidelines recommend this combination therapy for unfavorable scenarios, including oligoprogressive disease.
Conclusions:
- The combination of SABR and EGFR-TKIs represents a promising strategy to overcome resistance and improve outcomes in metastatic NSCLC.
- This combined approach is clinically recommended for managing oligometastatic and oligoprogressive disease in EGFR-mutated NSCLC patients.
