A Real-World Study of Patient Characteristics and Clinical Outcomes in IEGFR/I Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice

• Published in: Cancers 2024-03, Vol.16 (6)
• Main Authors: Viray, Hollis, Piper-Vallillo, Andrew J, Widick, Page, Academia, Emmeline, Shea, Meghan, Rangachari, Deepa, VanderLaan, Paul A, Kobayashi, Susumu S, Costa, Daniel B
• Format: Article
• Language: English
• Subjects: Epidermal growth factor; Lung cancer, Non-small cell; Patient outcomes; Pemetrexed; Pharmaceutical industry; Product development
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16061079

Cancer drug approvals are based on clinical trials with strict inclusion and exclusion criteria, and more often than not, the patient population encountered in real-world settings is different (with additional comorbidities or different patient-disease characteristics) than the one that led to regulatory approval. Oral inhibitors of the EGFR oncogene are approved for use in EGFR mutated lung cancers. We sought to evaluate if the EGFR inhibitor osimertinib would perform in real-word populations in a manner expected by the registration trial of this anti-cancer agent. We were able to identify cases in our real-world cohort that had durations of both cancer control and overall survival that were in line with the data from the registration clinical trial named FLAURA. The real-world data presented here support the translation of results from clinical trials to routine clinical care for targeted therapy in EGFR mutated lung cancer but also highlight the need for clinical trials that are more inclusive. Osimertinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that is used for first-line therapy in EGFR mutated non-small cell lung cancer (NSCLC) based on the results of the randomized FLAURA trial (ClinicalTrials.gov number NCT02296125). We performed a retrospective analysis of baseline characteristics and clinical outcomes in 56 real-world patients treated with osimertinib. In total, 45% of patients were determined to be FLAURA-eligible and 55% were FLAURA-ineligible based on the published inclusion/exclusion criteria of the aforementioned trial. For clinical outcomes, the median osimertinib time to treatment discontinuation (TTD) for all patients was 16.9 months (95% CI: 12.6–35.1), whereas the median TTD was 31.1 months (95% CI: 14.9–not reached) in the FLAURA-eligible cohort and the median TTD was 12.2 months (95% CI: 8.1–34.6 months) in the FLAURA-ineligible cohort. Re-biopsy at acquired resistance disclosed both on- and off-target mechanisms. The most common therapies following osimertinib included local therapies followed by post-progression osimertinib, platinum-doublet chemotherapy with or without osimertinib, and osimertinib combinatory targeted therapies. The median overall survival for all patients was 32.0 months (95% CI: 15.7–not reached), the median survival was not reached for the FLAURA-eligible cohort, and it was 16.5 months for the FLAURA-ineligible cohort. Our data support the use of osimertinib in real-word set