Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer
Yi-Long Wu1, Masahiro Tsuboi1, Jie He1
1From the Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, and Guangdong Academy of Medical Sciences, Guangzhou (Y.-L.W.), the Thoracic Surgery Department, National Cancer Center-National Clinical Research Center for Cancer-Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.H.), and the Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai (S.L.) - all in China; the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa (M.T.), and the Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama (T.K.) - both in Japan; the Department of Medical Oncology, Austin Health, Melbourne, VIC, Australia (T.J.); the Department of Respiratory Diseases, Evangelische Lungenklinik, Berlin (C.G.); the Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona (M.M.), and the Department of Oncology, Hospital Universitario Fundación Jiménez Díaz, Madrid (M.D.); the David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J.W.G.); the Center of Innovative Technologies and Oncology, N.N. Blokhin Russian Cancer Center, Russian Academy of Medical Sciences, Moscow (K.L.); the Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine (S.-W.K.), and the Precision Medicine Lung Cancer Center, Konkuk University Medical Center (K.-Y.L.) - both in Seoul, South Korea; the Department of Thoracic Surgery, Cho Ray Hospital, Ho Chi Minh City, Vietnam (H.-V.V.); the Division of Medical Oncology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand (C.A.); the Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-J.Y.); the Division of Thoracic Oncology, European Institute of Oncology, IRCCS, Milan (F.M.), and Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padua (L.B.) - both in Italy; the Department of Medical Oncology and Hematology, University Health Network, Princess Margaret Cancer Centre and the University of Toronto, Toronto (F.A.S.); Late Oncology Statistics, AstraZeneca, Gaithersburg, MD (L.Z.); Late Oncology Statistics (R.H.) and Oncology Research and Development (A.A., Y.R.), AstraZeneca, Cambridge, United Kingdom; and Section of Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, CT (R.S.H.).
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<0.001). In the overall population, 89% of the patients in the osimertinib group (95% CI, 85 to 92) and 52% of those in the placebo group (95% CI, 46 to 58) were alive and disease-free at 24 months (overall hazard ratio for disease recurrence or death, 0.20; 99.12% CI, 0.14 to 0.30; P<0.001). At 24 months, 98% of the patients in the osimertinib group (95% CI, 95 to 99) and 85% of those in the placebo group (95% CI, 80 to 89) were alive and did not have central nervous system disease (overall hazard ratio for disease recurrence or death, 0.18; 95% CI, 0.10 to 0.33). Overall survival data were immature; 29 patients died (9 in the osimertinib group and 20 in the placebo group). No new safety concerns were noted.
Conclusions:
In patients with stage IB to IIIA EGFR mutation-positive NSCLC, disease-free survival was significantly longer among those who received osimertinib than among those who received placebo. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).
Insights
Osimertinib significantly improved disease-free survival in patients with resected EGFR-mutated non-small-cell lung cancer (NSCLC). This adjuvant therapy demonstrated a notable reduction in disease recurrence or death compared to placebo.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Osimertinib is a standard treatment for advanced EGFR-mutated non-small-cell lung cancer (NSCLC).
- The role of osimertinib as adjuvant therapy in resected NSCLC was previously unestablished.
Purpose of the Study:
- To evaluate the efficacy and safety of adjuvant osimertinib in patients with completely resected EGFR-mutated NSCLC.
- To assess the impact of osimertinib on disease-free survival (DFS) and overall survival (OS).
Main Methods:
- A double-blind, phase 3 trial randomized 682 patients with resected EGFR-mutated NSCLC to receive either osimertinib (80 mg daily) or placebo for 3 years.
- The primary endpoint was DFS in patients with stage II-IIIA disease; secondary endpoints included DFS in stage IB-IIIA disease, OS, and safety.
- Patient randomization was conducted in a 1:1 ratio.
Main Results:
- At 24 months, 90% of stage II-IIIA patients on osimertinib were disease-free versus 44% on placebo (Hazard Ratio [HR] 0.17).
- In the overall IB-IIIA population, 89% of osimertinib-treated patients were disease-free at 24 months compared to 52% on placebo (HR 0.20).
- Central nervous system disease was significantly reduced with osimertinib (98% vs. 85% disease-free at 24 months).
Conclusions:
- Adjuvant osimertinib significantly improved DFS in patients with resected EGFR-mutated NSCLC (stage IB-IIIA).
- Osimertinib demonstrated a favorable safety profile with no new concerns identified.
- The study confirms osimertinib's efficacy as an adjuvant treatment for this patient population.
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