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Published on: November 22, 2021
Characterization of Patients with EGFR Mutation-Positive NSCLC Following Emergence of the Osimertinib Resistance
Mateo Sanchis-Borja1, Florian Guisier2, Aurélie Swalduz3
1Pulmonology Department, Créteil Intercommunal Hospital, Créteil, France.
Purpose:
The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib, is an effective first-line therapy for patients with common EGFR mutation-positive non-small cell lung cancer (NSCLC). However, almost all patients become resistant to treatment. In some patients, emergence of tertiary EGFR mutations is implicated as a resistance mechanism. This study describes patients with NSCLC who acquired the rare EGFR mutations, L718Q or G724S, following EGFR TKI treatment.
Patients And Methods:
This was a retrospective, observational study undertaken in France from Feb-Nov 2021, in patients with EGFR mutation-positive NSCLC with an acquired L718Q or G724S mutation. Primary objectives were description of tumor characteristics, progression, and progression under treatment.
Results:
Nine eligible patients were identified. Acquired resistance to initial EGFR TKI treatment was associated with T790M emergence in six patients, who then received osimertinib monotherapy. Overall, eight patients received osimertinib monotherapy treatment at some point (average treatment duration: 18.3 months). Following the emergence of L718Q or G724S, patients received chemotherapy (n = 4; two of whom subsequently received afatinib), nivolumab (n = 2), afatinib (n = 2), or immunochemotherapy (n = 1). In the four patients who received afatinib after identification of L718Q or G724S, 2 achieved a partial response, one had stable disease and one had progressive disease. Treatment duration was 1.6-31.7 months. In patients with controlled disease (n = 3), progression-free survival was 6.1-31.7 months. Two of these patients had previously received osimertinib.
Conclusion:
Currently, there is no consensus regarding the treatment of EGFR mutation-positive NSCLC following emergence of the osimertinib resistance mutations, L718Q or G724S. Afatinib appears to be a promising treatment option in this setting.
Insights
Osimertinib resistance in non-small cell lung cancer (NSCLC) can arise from rare EGFR mutations L718Q or G724S. Afatinib showed promise in treating NSCLC patients with these acquired resistance mutations.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Third-generation EGFR TKI osimertinib is a first-line therapy for EGFR mutation-positive NSCLC.
- Acquired resistance to osimertinib is a significant clinical challenge, often driven by tertiary EGFR mutations.
Observation:
- This study observed nine NSCLC patients who developed rare EGFR mutations L718Q or G724S after EGFR TKI treatment.
- Most patients initially developed T790M resistance before acquiring L718Q or G724S, subsequently receiving osimertinib monotherapy.
Findings:
- Following the emergence of L718Q or G724S mutations, patients were treated with chemotherapy, nivolumab, afatinib, or immunochemotherapy.
- In four patients treated with afatinib post-L718Q/G724S emergence, two achieved partial response, one had stable disease, and one had progressive disease.
Implications:
- There is no established treatment consensus for NSCLC with acquired L718Q or G724S mutations conferring osimertinib resistance.
- Afatinib demonstrates potential as a treatment option for NSCLC patients with these specific acquired EGFR resistance mutations.
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