Characterization of Patients with EGFR Mutation-Positive NSCLC Following Emergence of the Osimertinib Resistance Mutations, L718Q or G724S: A Multicenter Retrospective Observational Study in France

Abstract

Mateo Sanchis-Borja,1 Florian Guisier,2 Aurélie Swalduz,3 Hubert Curcio,4 Victor Basse,5 Christophe Maritaz,6 Christos Chouaid,1 Jean-Bernard Auliac1 1Pulmonology Department, Créteil Intercommunal Hospital, Créteil, France; 2Normandie Univ, UNIROUEN, LITIS Laboratory QuantIF team EA4108, CHU Rouen, Department of Pneumology and Inserm CIC-CRB 1404, Rouen, France; 3Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France; 4Department of Medical Oncology, Centre François Baclesse, Caen, France; 5Department of Oncology CHU Morvan, Brest, France; 6Medical Affairs Department, Oncology, Boehringer Ingelheim France, Paris, FranceCorrespondence: Jean-Bernard Auliac, Pulmonology Department, Créteil Intercommunal Hospital, Créteil, France, Email [email protected]: 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.Keywords: osimertinib, afatinib, real-world evidence, tertiary EGFR mutations

Keywords

• osimertinib
• afatinib
• real-world evidence
• tertiary egfr mutations