Osimertinib in patients with T790M mutation-positive, advanced non–small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies
Journal
Cancer
Journal Volume
125
Journal Issue
6
Pages
892-901
Date Issued
2019
Author(s)
Ahn M.-J
Tsai C.-M
Shepherd F.A
Bazhenova L
Sequist L.V
Hida T
Ramalingam S.S
Mitsudomi T
Jnne P.A
Mann H
Cantarini M
Goss G.
Abstract
Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is selective for both EGFR-TKI–sensitizing and T790M (threonine-to-methionine substitution at codon 790)-resistance mutations. The authors present long-term follow-up data from a preplanned, pooled analysis of phase 2 studies, the AZD9291 First Time in Patients Ascending Dose Study (AURA) extension trial (clincialtrials.gov identifier NCT01802632) and the AURA2 trial (NCT02094261). Methods: Patients with centrally confirmed, T790M mutation-positive, advanced non-small cell lung cancer received osimertinib 80 mg once daily until disease progression or study discontinuation. Response was assessed by a blinded, independent, central review using Response Evaluation Criteria in Solid Tumors, version 1.1. The primary endpoint was the objective response rate. Results: In total, 411 patients received osimertinib (second line, 129 patients; third line or later, 282 patients). At the data cutoff date of November 1, 2016, the median treatment exposure was 16.4 months (range, 0-29.7 months), the objective response rate was 66% (95% confidence interval [CI], 61%-70%), the median response duration was 12.3 months (95% CI, 11.1-13.8 months), and the median progression-free survival was 9.9 months (95% CI, 9.5-12.3 months). At the data cutoff date of May 1, 2018, 271 patients (66%) had died, and 140 patients (34%) had discontinued before death. The median overall survival was 26.8 months (95% CI, 24.0-29.1 months); and the 12-month, 24-month, and 36-month survival rates were 80%, 55%, and 37%, respectively. Grade ?3 possibly causally related (investigator assessed) adverse events were reported in 65 patients (16%), and the most common were rash (grouped terms; 42%; grade ?3, 1%) and diarrhea (39%; <1%). Conclusions: This pooled analysis represents the most mature clinical trial data for osimertinib in patients with pretreated, T790M-positive, advanced non-small cell lung cancer, further establishing osimertinib as a standard of care for this patient population. ? 2018 American Cancer Society
Subjects
AZD9291 First Time in Patients Ascending Dose Study (AURA); epidermal growth factor receptor (EGFR); osimertinib; pooled analysis; threonine-to-methionine mutation at codon 790 (T790M); tyrosine kinase inhibitor (TKI)
SDGs
Other Subjects
afatinib; antineoplastic agent; cetuximab; cytotoxic agent; dacomitinib; erlotinib; gefitinib; methionine; osimertinib; protein tyrosine kinase inhibitor; threonine; acrylamide derivative; aniline derivative; EGFR protein, human; epidermal growth factor receptor; osimertinib; protein kinase inhibitor; adult; advanced cancer; aged; anemia; Article; cancer growth; cancer mortality; cancer patient; cancer survival; cardiomyopathy; clinical assessment tool; diarrhea; disease severity; drug dose reduction; drug efficacy; drug safety; drug withdrawal; dry skin; female; follow up; gene mutation; heart failure; heart left ventricle ejection fraction; human; human cell; human tissue; leukopenia; lung edema; major clinical study; male; neutropenia; neutrophil count; non small cell lung cancer; open study; outcome assessment; overall survival; paronychia; phase 2 clinical trial; platelet count; pneumonia; priority journal; progression free survival; pruritus; QT prolongation; rash; reference value; side effect; stomatitis; survival rate; survival time; treatment response; clinical trial; drug administration; genetics; lung tumor; middle aged; mutation; non small cell lung cancer; oral drug administration; survival analysis; treatment outcome; very elderly; Acrylamides; Administration, Oral; Adult; Aged; Aged, 80 and over; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Protein Kinase Inhibitors; Survival Analysis; Treatment Outcome
Publisher
John Wiley and Sons Inc.
Type
journal article