Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1711-1723 |
| Number of pages | 13 |
| Journal | New Engl. J. Med. |
| Volume | 383 |
| Issue number | 18 |
| DOIs | |
| Publication status | Published - 2020 |
Keywords
- epidermal growth factor receptor
- osimertinib
- placebo
- acrylamide derivative
- aniline derivative
- antineoplastic agent
- protein kinase inhibitor
- acne
- adult
- aged
- Article
- cancer adjuvant therapy
- cancer free survival
- cancer prognosis
- cancer recurrence
- cancer staging
- controlled study
- coughing
- decreased appetite
- dermatitis
- diarrhea
- double blind procedure
- drug dose reduction
- drug efficacy
- dry skin
- EGFR gene
- female
- gene mutation
- human
- interstitial lung disease
- lung embolism
- lung lobectomy
- lung resection
- major clinical study
- male
- median survival time
- mouth ulcer
- non small cell lung cancer
- overall survival
- paronychia
- phase 3 clinical trial
- postoperative care
- priority journal
- pruritus
- quality of life
- randomized controlled trial
- recurrence risk
- rhinopharyngitis
- risk reduction
- stomatitis
- treatment duration
- upper respiratory tract infection
- adjuvant chemotherapy
- clinical trial
- disease free survival
- genetics
- lung tumor
- lymph node metastasis
- middle aged
- mortality
- multicenter study
- mutation
- tumor recurrence
- very elderly
- Acrylamides
- Adult
- Aged
- Aged, 80 and over
- Aniline Compounds
- Antineoplastic Agents
- Carcinoma, Non-Small-Cell Lung
- Chemotherapy, Adjuvant
- Disease-Free Survival
- Double-Blind Method
- ErbB Receptors
- Female
- Humans
- Lung Neoplasms
- Lymphatic Metastasis
- Male
- Middle Aged
- Mutation
- Neoplasm Recurrence, Local
- Neoplasm Staging
- Pneumonectomy
- Protein Kinase Inhibitors
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Osimertinib in resected EGFR-mutated non–small-cell lung cancer : New England Journal of Medicine. / Wu, Y.-L.; Tsuboi, M.; He, J. et al.
In: New Engl. J. Med., Vol. 383, No. 18, 2020, p. 1711-1723.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Osimertinib in resected EGFR-mutated non–small-cell lung cancer
T2 - New England Journal of Medicine
AU - Wu, Y.-L.
AU - Tsuboi, M.
AU - He, J.
AU - John, T.
AU - Grohe, C.
AU - Majem, M.
AU - Goldman, J.W.
AU - Laktionov, K.
AU - Kim, S.-W.
AU - Kato, T.
AU - Vu, H.-V.
AU - Lu, S.
AU - Lee, K.-Y.
AU - Akewanlop, C.
AU - Yu, C.-J.
AU - de Marinis, F.
AU - Bonanno, L.
AU - Domine, M.
AU - Shepherd, F.A.
AU - Zeng, L.
AU - Hodge, R.
AU - Atasoy, A.
AU - Rukazenkov, Y.
AU - Herbst, R.S.
N1 - Cited By :22 Export Date: 5 March 2021 CODEN: NEJMA Correspondence Address: Herbst, R.S.; Section of Medical Oncology, 333 Cedar St., P.O. Box 208028, United States; email: roy.herbst@yale.edu Correspondence Address: Wu, Y.-L.; Guangdong Lung Cancer Institute, China; email: syylwu@live.cn Correspondence Address: Tsuboi, M.; National Cancer Center Hospital East, 6 Chome-5-1 Kashiwanoha, Japan; email: mtsuboi@east.ncc.go.jp Chemicals/CAS: epidermal growth factor receptor, 79079-06-4; osimertinib, 1421373-65-0, 1421373-66-1; Acrylamides; Aniline Compounds; Antineoplastic Agents; ErbB Receptors; osimertinib; Protein Kinase Inhibitors Funding details: AstraZeneca Funding details: Merck Sharp and Dohme, MSD Funding details: Les Laboratories Pierre Fabre Funding details: Taiho Pharmaceutical Funding details: Chugai Pharmaceutical Funding details: Sanofi Funding details: Teijin Pharma Funding details: Pfizer Funding details: Bristol-Myers Squibb, BMS Funding details: Eli Lilly and Company Funding details: Roche Funding details: Bayer Fund, BF Funding details: Kyowa Kirin Pharmaceutical Development, KKD Funding details: Johnson and Johnson, J&J Funding details: Boehringer Ingelheim, BI Funding details: Astellas Pharma US Funding details: Spectrum Pharmaceuticals Funding details: Takeda Pharmaceuticals U.S.A., TPUSA Funding details: Roche Diagnostics Funding details: Shire Funding details: Shionogi Funding details: Dainippon Sumitomo Pharma Funding details: Merck Funding details: Genentech Funding details: Halozyme Funding text 1: The trial was funded by the sponsor and was designed by the investigators and the sponsor. The sponsor was responsible for collection and analysis of the data and had a role in data interpretation. The first draft of the manuscript was written by the first, second, and last authors, with medical-writing support funded by the sponsor and conducted in accordance with Good Publication Practice guidelines. All the authors had full access to the data, reviewed the manuscript before it was submitted for publication, and provided input. The authors vouch for the completeness and accuracy of the data and for the adherence of the trial to the protocol. Funding text 2: Supported by AstraZeneca. Funding text 3: Dr. Wu reports receiving grant support and lecture fees from AstraZeneca, Bristol-Myers Squibb, Pfizer, and Roche and lecture fees from Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, and Sanofi; Dr. Tsuboi, receiving lecture fees from Johnson & Johnson Japan, Teijin Pharma, Taiho Pharma, and Medtronic Japan, grant support, paid to his institution, lecture fees, and advisory board fees from AstraZeneca and Merck Sharp & Dohme, grant support, paid to his institution, and lecture fees from Eli Lilly Japan, Bristol-Myers Squibb, and Ono Pharmaceutical, lecture fees and advisory board fees from Chugai Pharmaceutical, grant support, paid to his institution, from Boehringer Ingelheim Japan, and advisory board fees from Novartis; Dr. John, receiving advisory board fees and travel support from Roche, advisory board fees from Bristol-Myers Squibb, Merck, Ignyta, Takeda, Specialised Therapeutics, Pfizer, Boehringer Ingelheim, and Bayer, and advisory board fees, lecture fees, and travel support from AstraZeneca and Merck Sharp & Dohme; Dr. Grohe, receiving advisory fees and speakers bureau fees from AstraZeneca and Merck Sharp & Dohme and advisory fees, speakers bureau fees, and travel support from Boehringer Ingelheim; Dr. Majem, receiving grant support and advisory board fees from Bristol-Myers Squibb, consulting fees, advisory board fees, lecture fees, and travel support from Merck Sharp & Dohme, advisory board fees, lecture fees, and travel support from Boehringer Ingelheim, AstraZeneca, Roche, and Kyowa Kirin, lecture fees from Pierre Fabre and Bayer, and advisory board fees from Takeda; Dr. Goldman, receiving grant support from AbbVie and Bristol-Myers Squibb, grant support and speakers bureau fees from Merck, and grant support, consulting fees, and advisory board fees from AstraZeneca; Dr. Kato, receiving grant support, advisory board fees, and lecture fees Funding text 4: from AbbVie, Amgen, Eli Lilly, Merck Biopharma, and Pfizer, grant support, advisory board fees, lecture fees, and scientific committee fees from AstraZeneca, Chugai Pharmaceutical, and Merck Sharp & Dohme, grant support and lecture fees from Bristol-Myers Squibb, Novartis, and Taiho Pharmaceutical, grant support, lecture fees, and scientific committee fees from Ono Pharmaceutical, lecture fees from Boehringer Ingelheim, F. Hoffmann–La Roche, and Shionogi, lecture fees and scientific committee fees from Daiichi Sankyo, advisory board fees from Nippon Kayaku, scientific committee fees from Nitto Denko, Sumitomo Dainippon Pharma, and Takeda, and grant support from Astellas, Kyorin Pharmaceutical, Kyowa Kirin, and Regen-eron Pharmaceuticals; Dr. Lu, receiving grant support, lecture fees, and consulting fees from AstraZeneca and Roche, grant support from Hutchison MediPharma, Bristol-Myers Squibb, and Heng Rui, lecture fees from Hansoh Pharmaceutical, and consulting fees from Boehringer Ingelheim, Hutchison Medi-Pharma, Simcere Pharmaceutical, Zai Lab, and GenomiCare Biotechnology; Dr. de Marinis, receiving advisory fees from Roche, Bristol-Myers Squibb, and AstraZeneca and consulting fees from Merck Sharp & Dohme; Dr. Domine, receiving lecture fees and advisory board fees from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, and Roche; Dr. Shepherd, receiving advisory board fees and owning stock in AstraZeneca; Dr. Zeng, being employed by and owning stock in AstraZeneca; Ms. Hodge, being employed by and owning stock in AstraZeneca; Dr. Atasoy, being employed by AstraZeneca; Dr. Rukazenkov, being employed by and owning stock in AstraZeneca; and Dr. Herbst, receiving consulting fees from AbbVie, ARMO BioSciences, Biodesix, Genmab, Halozyme Therapeutics, Heat Biologics, Loxo Oncology, Mirati Therapeutics, Nektar, NextCure, Oncternal Therapeutics, Pfizer, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro, Tocagen, and WindMIL Therapeutics, grant support, advisory board fees, and consulting fees from AstraZeneca, advisory board fees from Bolt Bio-therapeutics, Bristol-Myers Squibb, Cybrexa Therapeutics, I-Mab Biopharma, Immunocore, Infinity Pharmaceuticals, and Neon Therapeutics, grant support and consulting fees from Eli Lilly, Genentech–Roche, and Merck, data and safety monitoring committee fees from EMD Serono and Novartis, and board member fees from Junshi Pharmaceuticals. 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PY - 2020
Y1 - 2020
N2 - BACKGROUND Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation–positive advanced non–small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown. METHODS In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation–positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety. RESULTS A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P
AB - BACKGROUND Osimertinib is standard-of-care therapy for previously untreated epidermal growth factor receptor (EGFR) mutation–positive advanced non–small-cell lung cancer (NSCLC). The efficacy and safety of osimertinib as adjuvant therapy are unknown. METHODS In this double-blind, phase 3 trial, we randomly assigned patients with completely resected EGFR mutation–positive NSCLC in a 1:1 ratio to receive either osimertinib (80 mg once daily) or placebo for 3 years. The primary end point was disease-free survival among patients with stage II to IIIA disease (according to investigator assessment). The secondary end points included disease-free survival in the overall population of patients with stage IB to IIIA disease, overall survival, and safety. RESULTS A total of 682 patients underwent randomization (339 to the osimertinib group and 343 to the placebo group). At 24 months, 90% of the patients with stage II to IIIA disease in the osimertinib group (95% confidence interval [CI], 84 to 93) and 44% of those in the placebo group (95% CI, 37 to 51) were alive and disease-free (overall hazard ratio for disease recurrence or death, 0.17; 99.06% CI, 0.11 to 0.26; P
KW - epidermal growth factor receptor
KW - osimertinib
KW - placebo
KW - acrylamide derivative
KW - aniline derivative
KW - antineoplastic agent
KW - protein kinase inhibitor
KW - acne
KW - adult
KW - aged
KW - Article
KW - cancer adjuvant therapy
KW - cancer free survival
KW - cancer prognosis
KW - cancer recurrence
KW - cancer staging
KW - controlled study
KW - coughing
KW - decreased appetite
KW - dermatitis
KW - diarrhea
KW - double blind procedure
KW - drug dose reduction
KW - drug efficacy
KW - dry skin
KW - EGFR gene
KW - female
KW - gene mutation
KW - human
KW - interstitial lung disease
KW - lung embolism
KW - lung lobectomy
KW - lung resection
KW - major clinical study
KW - male
KW - median survival time
KW - mouth ulcer
KW - non small cell lung cancer
KW - overall survival
KW - paronychia
KW - phase 3 clinical trial
KW - postoperative care
KW - priority journal
KW - pruritus
KW - quality of life
KW - randomized controlled trial
KW - recurrence risk
KW - rhinopharyngitis
KW - risk reduction
KW - stomatitis
KW - treatment duration
KW - upper respiratory tract infection
KW - adjuvant chemotherapy
KW - clinical trial
KW - disease free survival
KW - genetics
KW - lung tumor
KW - lymph node metastasis
KW - middle aged
KW - mortality
KW - multicenter study
KW - mutation
KW - tumor recurrence
KW - very elderly
KW - Acrylamides
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aniline Compounds
KW - Antineoplastic Agents
KW - Carcinoma, Non-Small-Cell Lung
KW - Chemotherapy, Adjuvant
KW - Disease-Free Survival
KW - Double-Blind Method
KW - ErbB Receptors
KW - Female
KW - Humans
KW - Lung Neoplasms
KW - Lymphatic Metastasis
KW - Male
KW - Middle Aged
KW - Mutation
KW - Neoplasm Recurrence, Local
KW - Neoplasm Staging
KW - Pneumonectomy
KW - Protein Kinase Inhibitors
U2 - 10.1056/NEJMoa2027071
DO - 10.1056/NEJMoa2027071
M3 - Article
SN - 0028-4793
VL - 383
SP - 1711
EP - 1723
JO - New Engl. J. Med.
JF - New Engl. J. Med.
IS - 18
ER -