LBA1 - Osimertinib adjuvant therapy in patients (pts) with resected EGFR mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence

Background

CNS relapse is common in NSCLC, and is a poor prognostic factor. In the resected EGFRm NSCLC setting, the impact of treatment on sites of recurrence, including the CNS, is a key consideration. Osimertinib is a 3rd-generation EGFR-TKI with demonstrated efficacy in NSCLC CNS metastases. In ADAURA, osimertinib demonstrated a highly statistically significant and clinically meaningful improvement in disease-free survival vs placebo (PBO; DFS, hazard ratio [HR]: 0.20 [99.12% CI 0.14, 0.30; p<0.001) in resected stage IB–IIIA EGFRm (ex19del/L858R) NSCLC (Ph III ADAURA; NCT02511106). We report an exploratory analysis of recurrence patterns.

Methods

Pts with resected stage IB–IIIA EGFRm NSCLC, with/without adjuvant chemotherapy, were randomised 1:1 to receive osimertinib 80 mg once-daily or PBO until recurrence/discontinuation/3 years. Patterns of recurrence and CNS DFS (time to CNS recurrence/death) were exploratory endpoints. An MRI/CT brain scan was mandated at baseline either before surgery or upon enrolment, but was not required in absence of symptoms. Recurrence was categorised as local/regional and/or distant, with sites of relapse recorded. Data cutoff: 17/01/20.

Results

Overall, 682 pts were randomised (osimertinib: 339; PBO: 343). Pts treated with osimertinib had fewer recurrence events vs PBO (Table); 45 pts had CNS DFS events (osimertinib: 6; PBO: 39; median follow-up 22 months [mo]). Conditional probability of CNS recurrence at 12 mo (95% CI): <1% (0%, 2%) with osimertinib vs 7% (4%, 10%) with PBO. Median CNS DFS: not reached (95% CI 39.0 mo, not calculable [NC]) with osimertinib vs 48.2 (NC, NC) mo with PBO. CNS DFS HR: 0.18 (95% CI 0.10, 0.33); p<0.0001. Table: LBA1

*Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data. †Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.

Conclusions

There was a clinically meaningful improvement in CNS DFS with osimertinib: 82% reduction in risk of CNS disease recurrence or death. Results support that osimertinib reduces risk of CNS recurrence in the resected EGFRm NSCLC setting.

Clinical trial identification

NCT02511106.

Editorial acknowledgement

Natasha Learmond, BSC, of Ashfield Healthcare Communications, Macclesfield, UK, part of UDG Healthcare plc for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M. Tsuboi: Honoraria (self): Johnson & Johnson Japan; Honoraria (self), Research grant/Funding (institution): AstraZeneca KK; Honoraria (self): Eli Lilly Japan; Honoraria (self), Research grant/Funding (institution): Boehringer-Ingelheim Japan; Honoraria (self): Chugai Pharmaceutical Co., Ltd; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Bristol-Myers Squibb KK; Honoraria (self): Teijin Pharma; Honoraria (self): Taiho Pharma; Honoraria (self): Medtronic Japan; Honoraria (self): Ono Pharmaceutical Co., Ltd. Y-L. Wu: Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche. T. John: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Shareholder/Stockholder/Stock options: AstraZeneca; Honoraria (institution): Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Merck; Advisory/Consultancy: Ignyta; Advisory/Consultancy: Takeda; Advisory/Consultancy: MSD; Advisory/Consultancy: Specialised Therapeutics; Advisory/Consultancy: Pfizer. C. Grohe: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. M. Majem: Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self): MSD; Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Kyowa Kyrin; Honoraria (self): Pierre Fabre; Honoraria (self): Takeda; Honoraria (self): Bayer. J.W. Goldman: Speaker Bureau/Expert testimony: Merck; Honoraria (self), Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Merck; Research grant/Funding (self): BMS. S-W. Kim: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca. T. Kato: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Chugai; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy, Research grant/Funding (self): Merck Biopharma; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi-Sankyo; Advisory/Consultancy: Nippon Kayaku; Advisory/Consultancy: Nitto Denko; Advisory/Consultancy: Sumitomo Dainippon; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb; Research grant/Funding (self): Novartis; Research grant/Funding (self): Taiho; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: F.Hoffman-La Rohe; Speaker Bureau/Expert testimony: Shionogi. F. de Marinis: Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer. M. Domine: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche. F.A. Shepherd: Honoraria (self), Shareholder/Stockholder/Stock options: AstraZeneca. C. Yan, A. Atasoy: Full/Part-time employment: AstraZeneca. R. Herbst: Honoraria (self): AbbVie; Honoraria (self): Armo Biosciences; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self): Biodesix; Honoraria (self): Bolt Biotherapeutics; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self): Cybrexa; Honoraria (self): EMD Serrano; Honoraria (self), Research grant/Funding (self): Genentech/Roche; Honoraria (self): Genmab; Honoraria (self): Halozyme; Honoraria (self): Heat Biologics; Honoraria (self): IMAB Biopharma; Honoraria (self): Immunocore; Honoraria (self): Infinity Pharmaceuticals; Honoraria (self): Loxo Oncology; Honoraria (self), Research grant/Funding (self): Merck; Honoraria (self): Mirati Therapeutics; Honoraria (self): Nektar; Honoraria (self): Neon Therapeutics; Honoraria (self): NextCure; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Honoraria (self): Seattle Genetics; Honoraria (self): Shire PLC; Honoraria (self): Spectrum Pharmaceuticals; Honoraria (self): Symphogen; Honoraria (self): Takeda, Tesaro, Tocagen, WindMIL Therapeutics; Officer/Board of Directors: Junshi Pharmaceuticals. All other authors have declared no conflicts of interest.