356MO Osimertinib adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) NSCLC (ADAURA): Central nervous system (CNS) disease recurrence

Abstract

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. 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. 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: 356MOOsimertinib n=339PBO n=343CNS DFS events, pts (%):6 (2)39 (11)CNS recurrence4 (1)33 (10)Death*2 (1)6 (2)DFS events, pts (%):37 (11)159 (46)Disease recurrence37 (11)157 (46)—— Non-CNS recurrence33 (10)123 (36)—— CNS recurrence4 (1)33 (10)—— Disease recurrence with missing location01 (0)Death†02 (1)*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. Open table in a new tab *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. 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.