Osimertinib in Untreated EGFR -Mutated Advanced Non–Small-Cell Lung Cancer

Abstract

Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

“…Osimertinib has recently been evaluated in a first-line setting in the randomized Phase III trial, FLAURA [10]. In this study, patients with common (Del19/L858R) EGFR mutations were randomized to osimertinib or a firstgeneration EGFR TKI, whereby the specific EGFR TKI (erlotinib or gefitinib) was chosen by the site as the sole comparator prior to site initiation.…”

“…At data cutoff, OS data were immature (25%). Importantly, censoring of OS started at 15 months, which is when crossover from erlotinib/gefitinib to osimertinib may start to have an impact [10]; as such, the OS results are awaited with interest. Similar to the results from AURA and AURA3, plasma testing for EGFR mutations within the FLAURA trial showed good concordance with tissue testing, supporting the use of plasma testing in clinical practice to identify patients suitable for treatment [42].…”

Complications and Economic Burden Associated with Obtaining Tissue for Diagnosis and Molecular Analysis in Patients with Non-Small Cell Lung Cancer (NSCLC) in the US (Preprint)

“…However, the use of mandatory biopsies throughout a patient's treatment is expected to increase as biomarker-driven drug approvals become the norm [16]. Osimertinib is a third-generation, EGFR-TKI that potently and selectively inhibits both EGFR sensitizing and EGFR T790M resistance mutations [5,17,18]. Based on positive results from the AURA trial program and FLAURA first-line study, osimertinib is recommended in the US as a first-line treatment option for patients with EGFR mutation-positive advanced NSCLC and as a second-line treatment for patients with T790M-positive NSCLC following disease progression on a first-line EGFR-TKI therapy (erlotinib, gefitinib, or afatinib) [12,19].…”

“…Although tumor tissue samples remain the gold standard for cancer mutation testing, novel methods of testing are emerging that are less invasive, including those based on cytology samples and ctDNA which should be considered for patients who are ineligible for a tissue biopsy. Various studies support the use of plasma ctDNA samples for the detection of EGFR mutations at diagnosis of NSCLC, including data from the recent AURA (AURA extension, AURA2, and AURA3) and FLAURA studies [18,31,32,17]. The phase I AURA post-hoc analysis (NCT01802632) found that, in patients with advanced NSCLC and EGFR T790M-positive status (according to central tumor genotyping), the sensitivity of plasma ctDNA samples for the detection of T790M was 70% [32].…”

Central nervous system penetration and efficacy of targeted therapies used in non-small cell lung cancer and melanoma with brain metastases

“…All these results stated that osimertinib had a prolonged progression free survival than the current standard EGFR mutation-positive treatment. [15] 2.2 ALK inhibitors 2.2.1 Crizotinib Crizotinib is FDA approved for metastatic NSCLC ALK+ mutations. It binds to ATP in a competitive manner, which results in binding and inhibition of ALK kinase and ALK fusion proteins.…”