Optimizing Treatment Strategies for Egfr-Mutated Non-Small-Cell Lung Cancer Treated with Osimertinib: Real-World Outcomes and Insights

Quentin Dominique Thomas; Nicolas Girard; Lise Bosquet; Sarah Cavaillon; Thomas Filleron; Siham Eltaief; Christos Chouaid; Hervé Lena; Didier Debieuvre; Maurice Perol; Xavier Quantin

doi:10.3390/cancers16213563

Optimizing Treatment Strategies for Egfr-Mutated Non-Small-Cell Lung Cancer Treated with Osimertinib: Real-World Outcomes and Insights

Cancers (Basel). 2024 Oct 23;16(21):3563. doi: 10.3390/cancers16213563.

Authors

Affiliations

¹ Department of Medical Oncology, Institut du Cancer de Montpellier, 34000 Montpellier, France.
² Department of Medical Oncology, Institut Curie, 75005 Paris, France.
³ Unicancer, 75000 Paris, France.
⁴ Biostatistics Unit, Oncopôle Claudius Régaud IUCT-O, 31100 Toulouse, France.
⁵ Department of Pneumology, Centre Hospitalier Intercommunal, 94010 Créteil, France.
⁶ Pneumology Department, CHU Pontchaillou, 35000 Rennes, France.
⁷ Respiratory Medicine Department, Groupe Hospitalier de la Région Mulhouse Sud-Alsace, 68100 Mulhouse, France.
⁸ Department of Medical Oncology Centre Léon Bérard, 69008 Lyon, France.

Abstract

Background: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), demonstrated superior efficacy over first-generation TKIs in the FLAURA trial, resulting in its approval as first-line therapy for metastatic non-small-cell lung cancer (NSCLC). However, the real-world application of these trial results requires an evaluation of sequential therapeutic strategies. Methods: This retrospective, non-interventional study utilized data from the Epidemiological Strategy and Medical Economics (ESME) platform, which includes information on patients treated for lung cancer since 2015. Out of 39,974 patients in the database, 624 patients with EGFR-mutant advanced NSCLC treated with osimertinib as first-line (L1, n = 198) or second-line (L2, n = 426) treatment after first- or second-generation TKIs (n = 1262) were identified. Patient demographics, disease characteristics, treatment strategies, and disease progression were examined. Survival analyses were performed using Kaplan-Meier estimates and Cox proportional-hazards models. Results: In the study population (n = 624), 73.4% were female, with a median age of 70 years (range 28-93). Brain metastases at the start of osimertinib treatment were observed in 282 patients. ECOG PS-2 was reported in 29.4% of patients. The T790M mutation in exon 20 was identified in 257/426 patients (60.3%) receiving osimertinib in L2. Median progression-free survival (PFS) was 12.4 months (95% CI [10.7-14.7]) for L1 and 7.4 months (95% CI [6.2-8.7]) for L2. Median overall survival (OS) from advanced diagnosis was 28.5 months (95% CI [26.3-38.7]) for osimertinib L1 and 29.9 months (95% CI [28.6-31.8]) for osimertinib L2 (HR = 0.93; 95% CI [0.75-1.16]; p = 0.50). For L1, median OS was 27.1 months (95% CI [22.0-30.2]) for patients with cerebral metastases and 38.7 months (95% CI [26.3-52.8]) for those without (HR = 0.73; 95% CI [0.48-1.11]; p = 0.15). Discussion: Patients in the real-world ESME database exhibited a poorer prognosis compared to those in the FLAURA trial. The presence of cerebral metastases at diagnosis worsens the prognosis.

Keywords: EGFR mutation; brain metastasis; non-small-cell lung cancer; treatment sequencing; tyrosine kinase inhibitors.

Grants and funding

This work was supported by Unicancer. Unicancer independently manages ESME databases (i.e., data collection, analysis, and publication) and is the sole data controller for data processing. The ESME LC database receives financial support from industrial partners (Astrazeneca, Pfizer, Janssen, Amgen, Roche, Merck Sharp & Dohme, Bristol-Meyers Squibb, and Daiichi Sankyo). Janssen specifically funded this work.