Representativeness of Phase III Trial for Osimertinib in Pretreated Advanced EGFR-Mutated Non-small-cell Lung Cancer Patients and Treatment Outcomes in Clinical Practice

• Published in: Targeted oncology Vol. 17; no. 1; pp. 53 - 59
• Main Authors: Lin, Lishi, Smit, Egbert F., de Langen, Adrianus J., van Balen, Dorieke E. M., Beijnen, Jos H., Huitema, Alwin D. R.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2022; Springer Nature B.V
• Subjects: Acrylamides; Aniline Compounds - pharmacology; Aniline Compounds - therapeutic use; Biomedicine; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemotherapy; Clinical outcomes; Drug dosages; ErbB Receptors - genetics; ErbB Receptors - therapeutic use; Humans; Lung cancer; Lung Neoplasms - drug therapy; Medicine; Medicine & Public Health; Metastasis; Mutation; Oncology; Original; Original Research Article; Patients; Pharmacy; Retrospective Studies; Targeted cancer therapy; Treatment Outcome
• ISSN: 1776-2596; 1776-260X
• DOI: 10.1007/s11523-021-00862-x

Background Overall survival (OS) data of osimertinib in pretreated non-small-cell lung cancer (NSCLC) in real-world practice is limited, and treatment benefits for patients not represented in the pivotal trials (ineligible) are unclear. Objective To determine the representativeness of the AURA3 trial for NSCLC patients treated with osimertinib in a real-world setting and to determine outcomes of patients who were represented in the AURA3 trial (eligible) and those who were ineligible. Methods Advanced NSCLC patients receiving post first-line osimertinib were included in this retrospective study and were divided into two groups based on eligibility criteria of the AURA3 trial. Progression-free survival (PFS) and OS were estimated using the Kaplan–Meier method. Cox models were used to estimate the association of eligibility criteria with OS. Results 328 patients were included; 126 (38%) patients were eligible and 202 (62%) patients were ineligible. The most common ineligibility reasons were the number of earlier treatment lines and an Eastern Cooperative Oncology Group performance status (ECOG PS) > 1. PFS of eligible and ineligible patients was not statistically different (8.0 vs. 5.8 months, p  = 0.062). Eligible patients had a longer OS (24.0 vs. 15.4 months, p  = 0.001) compared to ineligible patients. ECOG PS was the best predictor for OS. An ECOG PS of 1 was already associated with poorer survival compared to an ECOG PS of 0 (hazard ratio 1.54; p  = 0.016). Conclusion The majority of the study population was not represented in the AURA3 trial. Survival outcomes of eligible patients are in concordance with the AURA3 trial, while OS of ineligible patients was significantly shorter compared to eligible patients.