356MO - 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: 356MO

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