Introduction: Here we report efficacy and safety data of an Asian subset of the phase III FLAURA trial (NCT02296125), which compares osimertinib with standard of care (SoC) EGFR tyrosine kinase inhibitors (TKIs) in patients with previously untreated advanced NSCLC with tumors harboring exon 19 deletion (Ex19del)/L858R EGFR TKI–sensitizing mutations. Methods: Eligible Asian patients (enrolled at Asian sites) who were at least 18 years of age (≥20 years in Japan) and had untreated EGFR-mutated advanced NSCLC were randomized 1:1 to receive osimertinib (80 mg, orally once daily) or an SoC EGFR TKI (gefitinib, 250 mg, or erlotinib, 150 mg, orally once daily). The primary end point was investigator-assessed progression-free survival (PFS). The key secondary end points were overall survival, objective response rate, central nervous system efficacy, and safety. Results: The median PFS was 16.5 versus 11.0 months for the osimertinib and SoC EGFR TKI groups, respectively (hazard ratio = 0.54, 95% confidence interval: 0.41–0.72, p < 0.0001). The overall survival data were immature (24% maturity). The objective response rates were 80% for osimertinib and 75% for an SoC EGFR TKI. The median central nervous system PFS was not calculable for the osimertinib group and was 13.8 months for the SoC EGFR TKI group (hazard ratio = 0.55, 95% confidence interval: 0.25–1.17, p = 0.118). Fewer adverse events of grade 3 or higher (40% versus 48%) and fewer adverse events leading to treatment discontinuation (15% versus 21%) were reported with osimertinib versus with an SoC EGFR TKI, respectively. Conclusion: In this Asian population, first-line osimertinib demonstrated a clinically meaningful improvement in PFS over an SoC EGFR TKI, with a safety profile consistent with that for the overall FLAURA study population.
Bibliographical noteFunding Information:
Disclosure: Dr. Dechaphunkul has declared research funding from AstraZeneca, Novartis, Roche, and Merck Sharp and Dohme. Dr. Chewaskulyong has declared research funding from AstraZeneca, Merck, Merck Sharp and Dohme, Roche, and Samsung Bioepis. Dr. Cho has declared research funding from Novartis, AstraZeneca, MOGAM Institute, Dong-A ST, Abbvie, Janssen, Yuhan, and Champions Oncology and has worked in a consulting role for Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Yuhan, Pfizer, Eli Lilly and Company, Yuhan, and Ono Pharmaceutical Co., Ltd. Dr. Zhou has received honoraria for lectures from Eli Lilly and Company, AstraZeneca, Boehringer Ingelheim, Roche, and Sanofi and has declared research funding from Pfizer and Boehringer Ingelheim. Dr. Imamura has declared research funding and received honoraria from Taiho Pharmaceutical Company, Pfizer, Inc., AstraZeneca K. K., Novartis Pharma K. K., Boehringer Ingelheim GmbH, Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K. K., Chugai Pharmaceutical Co. Ltd., Bristol-Myers Squibb. and Merck Sharp and Dohme. Ms. Mann is an employee of AstraZeneca. Dr. Okamoto reports grant support from AstraZeneca during the conduct of the study, as well as grant support and personal fees from AstraZeneca, ONO, Bristol-Myers Squibb, Chugai, Eli Lilly and Company, Taiho, Boehringer Ingelheim, and Pfizer outside the submitted work. Dr. Saggese is an employee of AstraZeneca. Dr. Nogami has received honoraria from AstraZeneca, Chugai Pharmaceutical Co. Ltd., Pfizer Japan Inc., Eli Lilly Japan K.K., Ono Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co. Ltd, Merck Sharp and Dohme, and Bristol-Myers Squibb. Dr. Ramalingam has received honoraria for scientific advisory board meetings from AstraZeneca, Amgen, Abbvie, Bristol-Myers Squibb, Merck, Genentech, Takeda, Roche, Eli Lilly and Company, and Loxo Oncology. Dr. Kurata has received a research grant from AstraZeneca and honoraria from AstraZeneca, Merck Sharp and Dohme Eli Lilly and Company, Chugai, Ono, Bristol-Myers Squibb, and Boehringer Ingelheim. Dr. Reungwetwattana has declared research funding from AstraZeneca, Novartis, Roche, and Merck Sharp and Dohme. Dr. Sriuranpong has received speaker fees from AstraZeneca, Novartis, Roche, Pfizer, Sanofi, Merck, Eisai, Boehringer Ingelheim, Taiho, and Janssen; declared honoraria for participation on advisory boards for Merck Sharp and Dohme, Novartis, Pfizer, Roche, Eisai, and Merck; and received research grants from AstraZeneca, Novartis, Roche, Pfizer, Sanofi, Boehringer Ingelheim, Eisai, Taiho, Eli Lilly and Company, and Bristol-Myers Squibb. Dr. Ohe has received grants and personal fees from AstraZeneca during the conduct of the study, as well as grants and personal fees from Chugai, Bristol-Myers Squibb, Eli Lilly and Company, Taiho, Pfizer, Merck Sharp and Dohme, and Novartis; in addition, Dr. Ohe has received grants from Kyorin and Dainippon-Sumitomo and personal fees from Boehringer Ingelheim and Bayer outside the submitted work. The remaining authors declare no conflict of interest.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This work was supported by AstraZeneca , the manufacturer of osimertinib. Thanks to all the patients and their families. The study ( NCT02296125 ) was funded by AstraZeneca , the manufacturer of osimertinib. The authors would like to acknowledge Natalie Griffiths, PhD, from iMed Comms, Macclesfield, United Kingdom, an Ashfield Company and part of UDG Healthcare plc, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines ( http://www.ismpp.org/gpp3 ).
© 2018 International Association for the Study of Lung Cancer
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine