Adjuvant osimertinib therapy in patients with resected EGFR-mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC): updated ADAURA results

Background: Osimertinib is a third-generation epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI sensitising and EGFR T790M resistance mutations. It has efficacy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC), including in central nervous system (CNS) metastases. In the Phase III ADAURA (NCT02511106) primary analysis adjuvant osimertinib showed a significant and clinically meaningful disease-free survival (DFS) benefit vs placebo (PBO) in patients with completely resected EGFRm (ex19del/L858R) NSCLC, ± adjuvant chemotherapy: stage IIꟷIIIA DFS hazard ratio (HR), 0.17; 99.06% confidence interval (CI), 0.11, 0.26; p<0.0001; stage IBꟷIIIA DFS HR, 0.20; 99.12% CI 0.14, 0.30; p<0.0001. We report updated exploratory analyses of DFS and recurrence patterns after 2 years added follow up.

Methods: Eligible patients (aged ≥18 years [≥20 in Japan/Taiwan], World Health Organisation performance status 0/1, completely resected EGFRm stage IBꟷIIIA [American Joint Committee on Cancer 7th edition] NSCLC; adjuvant chemotherapy allowed) were randomized 1:1 to osimertinib 80 mg once daily or PBO for up to 3 years. Primary endpoint: investigator-assessed DFS in stage IIꟷIIIA. Secondary endpoints: DFS in stage IBꟷIIIA, overall survival and safety. Patterns of recurrence and CNS DFS were pre-specified exploratory endpoints. Data cut-off: 11 April 2022.

Results: Globally, 682 patients were randomized; osimertinib n=339, PBO n=343. In this updated analysis, in patients with stage IIꟷIIIA disease DFS HR was 0.23 (95% CI 0.18, 0.30; 242/470 events; 51% maturity); 3 year DFS rate was 84% with osimertinib vs 34% with PBO. In the overall population (stage IBꟷIIIA) DFS HR was 0.27 (95% CI 0.21, 0.34; 305/682 events); 3 year DFS rate was 85% with osimertinib vs 44% with PBO. In the osimertinib arm, fewer patients experienced local/regional and distant recurrence vs PBO. CNS DFS HR was 0.24 (95% CI 0.14, 0.42; 63/470 events) in stage IIꟷIIIA. The long-term safety profile remains consistent with the known profile of osimertinib.

Conclusions: With 2 years further follow-up, a continued DFS benefit was sustained with osimertinib vs PBO, consistent with the primary analysis. These mature data reinforce adjuvant osimertinib as standard of care for patients with EGFRm stage IB–IIIA NSCLC after complete tumour resection and adjuvant chemotherapy, when indicated. (ENCORE)

Previously presented at ESMO 2022, Final Publication Number: LBA47, Masahiro Tsuboi et al. - Reused with permission.

Masahiro Tsuboi (1), Yi-Long Wu (2), Christian Grohe (3), Thomas John (4), Margarita Mmajem@santpau.catac.org (5), Jie Wang (6), Terufumi kato (7), Jonathan Goldman (8), Sang-We Kim (9), Chong-Jen Yu (10), Huu Vinh Vu (11), Guzel Mukhametshina (12), Charuwan Akewanlop (13), Filippo de Marinis (14), Frances Sherpherd (15), Damien Urban (16), Marta Stachowiak (17), Ana Bolanos (18), Xiangning Huang (19), Roy Herbst (20), (1) Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan, (2) N/A, N/A, (3) 3Klinik für Pneumologie - Evangelische Lungenklinik Berlin Buch, Berlin, (4) Austin Health, Melbourne, (5) Hospital de la Santa Creu i Sant Pau, Barcelona, (6) Chinese Academy of Medical Sciences, Bejing, (7) Kanagawa Cancer Center, Yokoham, (8) University of California Los Angeles, Los Angeles, CA, (9) Asan Medical Center, Seoul, (10) National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, (11) Cho Ray Hospital, Ho Chi Minh City, (12) Republican Clinical Oncology Center, Republic of Tatarstan, (13) Siriraj Hospital, Bangkok, (14) European Institute of Oncology, Milan, (15) University Health Network, Toronto, (16) Tel-Aviv University, Tel-Aviv, (17) AstraZeneca, Warsaw, (18) AstraZeneca, Mississauga, (19) AstraZeneca, Cambridge, (20) Smilow Cancer Hospital at Yale New Haven, New Haven, CT

James Isbell

Invited Discussant

James M. Isbell, MD, MSCI completed his medical degree at the University of Texas Southwestern Medical School, his general surgery residency at Vanderbilt University Medical Center, his cardiothoracic training at the University of Virginia and surgical critical care training at the University of Virginia and Johns Hopkins. Dr. Isbell is an Associate Professor with dual appointments in the Department of Surgery and the Department of Anesthesiology and Critical Care Medicine at Memorial Sloan Kettering Cancer Center in New York, NY. In addition to his active thoracic surgical practice, he occasionally attends in MSK's ICU and enjoys clinical and translational research. Dr. Isbell leads multiple clinical trials in thoracic oncology. His translational research is focused on the use of liquid biopsy in the diagnosis, treatment and prognosis of lung cancer. He leads an AATS-TSOG-sponsored multicenter study evaluating the predictive and prognositc value of longitudinally monitoring ctDNA levels in patients undergoing neoadjuvant therapy followed by surgical resection for non-small cell lung cancer.  He serves as the Director of Quality and Outcomes for the MSK Thoracic Surgery Service, Co-Director of the MSK's Thoracic Liquid Biopsy Progam and Director of MSK's Step-Down Units.  He also currently serves as a member of the AATS Thoracic Quality Committee.  

Masahiro Tsuboi

Abstract Presenter

Dr Masahiro Tsuboi is a chair and a director of department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan, Visited associate professor, Department of Thoracic Surgery & Oncology, Tokyo Medical University, Tokyo, Japan and a visiting professor, Department of Surgery, Yokohama City University Graduate school of Medicine, Yokohama, Japan

Dr Tsuboi is a past board director of International Association for the Study of Lung Cancer (IASLC), a past chair of the Lung Cancer Surgical Study Group (LCSSG) of the Japan Clinical Oncology Group (JCOG), and a past board director of World Association of Bronchology and Interventional Pulmonology (WABIP).

Dr Tsuboi is involved in numerous perioperative adjuvant and surgical clinical trials, such as JCOG0707: Tegaful-Uracil vs. S-1 in adjuvant setting for stage IA3-IB NSCLC, JIPANG: cisplatin+vinorelbine vs. cisplatin+pemetrexed in the adjuvant setting for stage II-III NSCLC,  JCOG0804/WJOG4507L: sublobar resection for small-size peripheral lung adenocarcinoma, and JCOG0802/WJOG4607L:  Segmentectomy versus lobectomy in small-sized peripheral non-small cell lung cancer, as a primary investigator or a member of the steering committee. He is a co-global primary investigator of the ADAURA trial, and the Neo-ADAURA trial.

His specialty and research fields of interest: 1) Surgical and Medical Oncology for Thoracic Malignancies, 2) Clinical trials for Thoracic Malignancies, 3) Combined Modality Treatment for Lung Cancer and mesothelioma, 4) Extended radical surgery including salvage surgery after the definitive treatment

Specialties: Thoracic, Anatomy and Conditions, Lung--Cancer, Treatment/Procedure/Operation/Surgery, Lung--Cancer