Osimertinib (osi) is a 3rd-gen CNS active EGFR-TKI for EGFRm NSCLC. In the Ph III ADAURA (NCT02511106) primary analysis adjuvant osi showed a significant DFS benefit vs placebo (PBO) in resected EGFRm NSCLC, with a low frequency of osi dose modifications/discontinuations and no new safety signals observed. We report exploratory analyses of long-term safety data from ADAURA.
Eligible patients (pts; completely resected EGFRm stage IB–IIIA [AJCC 7th edition] NSCLC ± adjuvant CT) were randomised (682 globally) 1:1 to osi 80 mg QD or PBO for up to 3 yrs. Safety assessments were performed at baseline, wk 2, 4 and 12, then every 12 wks until treatment was completed/discontinued, and at day 28 after treatment stopped. Post hoc analyses of most common/AEs of clinical interest over time, and a summary of AEs by sex, were exploratory. DCO: 11 April 2022.
The safety set included: osi n=337; PBO n=343. Median duration of treatment exposure was 35.8 (osi) and 25.1 (PBO) months. The majority of pts in both arms reported an AE (any) with first onset between 0–12 months (osi 97%, PBO 86%). The proportion of pts reporting AEs with first onset after 12 months was low (osi 1%, PBO 4%). Dose interruptions/reductions/discontinuations of treatment due to AEs were 27/12/13% with osi and 13/1/3% with PBO. Stomatitis was the most common AE leading to dose reduction (osi 3%, PBO 0%); diarrhoea was the most common leading to interruption (osi 4%, PBO 1%). ILD was reported in 11 pts (3%; all Gr 1/2) in the osi arm and no pts in the PBO arm, and was the most common AE leading to discontinuation (osi 3%). The incidence of AEs (any), SAEs and AEs leading to discontinuation were similar between male and female pts. All fatal AEs were considered unrelated to treatment: osi n=1 (respiratory failure); PBO n=2 (pulmonary embolism, unknown AE).
Osi was well tolerated over a prolonged treatment duration. Most AEs developed within the first 12 months of treatment, with a low proportion first reported after 12 months. There was no meaningful difference in AE incidence by sex. Combined with significant efficacy benefit, these data support long-term treatment with osi as standard of care in EGFRm stage IB–IIIA resected NSCLC.
NCT02511106.
The authors would like to acknowledge Rachel Gater, PhD, of Ashfield MedComms, an Inizio company for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
AstraZeneca.
AstraZeneca.
T. John: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Ignyta, Novartis, Bayer. C. Grohe: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel Fees: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme. J.W. Goldman: Financial Interests, Personal, Other, Research Support: Advaxis, Array, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Genentech, G1 Therapeutics, Merck, Pfizer; Financial Interests, Personal, Other, Travel Fees: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Genentech, Pfizer. F. de Marinis: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Novartis, Pfizer, Takeda, Roche, MSD, X-Covery. T. Kato: Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Merck Serono, Merck Sharp & Dohme, Pfizer, Daiichi-Sankyo; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Merck Serono, Merck Sharp & Dohme, Pfizer, Bristol Myers Squibb, Novartis, Taiho Pharmaceutical, Boehringer Ingelheim, Roche; Financial Interests, Personal, Full or part-time Employment, Spouse: Eli Lilly and Company; Financial Interests, Personal, Other, Research Support: AstraZeneca, Amgen Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly and Company, Merck Serono, Merck Sharp & Dohme, Pfizer, Novartis, AbbVie Inc., Regeneron. J. Choi: Financial Interests, Personal, Other, Research Support: AstraZeneca, Roche, Samyang Biopharmaceuticals Corporation (Korea), Yuhan Corporation (Korea). B. Melotti: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharmaceutical Industries Ltd.; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharmaceutical Industries Ltd.; Financial Interests, Personal, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Novartis, Roche, Sanofi. M.D. Fidler: Financial Interests, Personal, Advisory Role: AstraZeneca, BeiGene, Biodesix, Daiichi Sankyo, G1 Therapeutics, Genentech, Janssen, Gilead, Jazz Pharmaceuticals, Rakuten, Silverback Therapeutics; Financial Interests, Personal, Other, Research Support: Alkermes, Astellas, AstraZeneca, Biodesix, Genentech, Pfizer, Rakuten; Financial Interests, Personal, Writing Engagements: Gilead. L. Sainsbury: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Stachowiak: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S. Taggart: Financial Interests, Personal, Full or part-time Employment: Exploristics; Financial Interests, Personal, Full or part-time Employment, Contracted: AstraZeneca. Y. Wu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Takeda; Financial Interests, Personal, Other, Research Support: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Hengrui, Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Beigen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Pfizer, Roche, Sanofi. M. Tsuboi: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck Sharp & Dohme, Novartis, Chugai Pharmaceutical Co. Ltd.; Financial Interests, Personal, Other, Research Support: Boehringer Ingelheim, Merck Sharp & Dohme, AstraZeneca, Ono Pharmaceuticals Co. Ltd., Bristol Myers Squibb, Eli Lilly and Company, Novartis, MIRXES Japan; Financial Interests, Personal, Invited Speaker: Johnson & Johnson, AstraZeneca, Eli Lilly and Company, Chugai Pharmaceuticals Co. Ltd., Taiho Pharma, Medtronic Japan Co., Ltd., Ono Pharmaceutical Co. Ltd., Merck Sharp & Dohme, Bristol Myers Squibb, Teijin Pharma. R.S. Herbst: Financial Interests, Personal, Advisory Role: AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Candel Therapeutics, Inc., Checkpoint Therapeutics, Cybrexa Therapeutics, DynamiCure Biotechnology, LLC, eFFECTOR Therapeutics, Inc., Eli Lilly and Company, EMD Serono, Genentech, Gilead, HiberCell, Inc., I-Mab Biopharma, Immune-Onc Therapeutics, Inc., Immunocore, Janssen, Johnson and Johnson, Loxo Oncology, Mirati Therapeutics, NextCure, Novartis, Ocean Biomedical, Inc., Oncocyte Corp, Oncternal Therapeutics, Pfizer, Regeneron Pharmaceuticals, Revelar Biotherapeutics, Inc., Ribbon Therapeutics, Roche, Sanofi, Xencor, Inc; Financial Interests, Personal, Research Grant: AstraZeneca, Eli Lilly and Company, Genentech/Roche, Merck and Company; Financial Interests, Personal, Leadership Role: American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, Southwest Oncology Group; Financial Interests, Personal, Member of the Board of Directors, (non-executive/independent): Immunocore, Junshi Pharmaceuticals. M. Majem Tarruella: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca; Financial Interests, Personal, Other, Research Support: Bristol Myers Squibb, Roche, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Pfizer, Helsinn, Sanofi, Mundipharma, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Roche, Kyowa Kyrin, Pierre Fabre, Takeda, Bayer, Amgen Inc. All other authors have declared no conflicts of interest.