Aumolertinib activity in patients with CNS metastases and EGFR-mutated NSCLC treated in the randomized double-blind phase III trial (AENEAS).

Abstract

9096 Background: We previously reported (Lu, ASCO 2021, abstract # 9013) that treatment with aumolertinib (Au), a 3rd generation EGFR TKI, led to robust improvement in progression free survival (PFS) (median PFS 19.3 to 9.9 months, HR = 0.46, p < 0.0001) when compared to gefitinib (G) with a predictable and encouraging safety profile. This benefit was maintained across all prespecified stratification factors including the subset of ̃ 27% of patients (pts) with CNS metastases (HR = 0.38). Here we undertook this analysis to more fully characterize the activity and benefit of Au as compared to G in this clinically important subset of EGFR mutant NSCLC pts. Methods: Pts with previously untreated metastatic or locally advanced NSCLC with EGFR sensitizing mutations were enrolled and randomly assigned in a 1:1 ratio to receive either Au (110 mg QD) or G (250 mg QD). Predefined stratification factors were EGFR-mutated status (Ex19del vs L858R) and CNS metastases (yes vs no). Patients with stable, asymptomatic CNS metastases were eligible for enrollment. All pts had baseline brain imaging by magnetic resonance imaging or computed tomography. The primary endpoint was PFS assessed by investigator per RECIST v1.1 in full analysis set (systemic analysis). Independent CNS efficacy was performed both in pts with baseline CNS metastases (CNS full analysis set, cFAS) and in pts with baseline CNS target lesions (CNS evaluable-for-response set, cEFS) by blinded independent central neuroradiology review (BICR) per RECIST v1.1. Results: Of 429 pts, 106 pts (Au, n = 51; G, n = 55) were found to have CNS metastases (cFAS) and 61 pts (Au, n = 29; G, n = 32) had CNS target lesions as defined by RECIST 1.1 (cEFS) at baseline by BICR. At the cutoff date (Aug 6, 2021), based on cEFS, CNS PFS events were observed in 11 pts (38%) treated with Au versus 20 pts (63%) who were randomized to receive G. Treatment with Au significantly prolonged CNS median PFS compared with G (29.0 vs 8.3 months; HR = 0.300; 95% CI, 0.137-0.657; P = 0.0015). Estimated CNS PFS rate at 12 and 18 months were 71% and 62% in Au arm compared with 23% and 0% in G arm. The confirmed CNS ORR were 82.8% and 75.0% in pts treated with Au and G, respectively (odds ratio = 1.600; 95% CI, 0.457-5.597; P = 0.4621). Au also achieved longer CNS median PFS over G in cFAS (29.0 vs 8.3 months; HR = 0.323; 95% CI, 0.181-0.576; P < 0.0001). No new safety findings were observed. Conclusions: Au demonstrated superior clinical efficacy against CNS metastases over G as first-line therapy in EGFR-mutated advanced NSCLC, and the safety profile was consistent with that reported previously. Additional randomized studies of Au in pts with CNS metastases are ongoing (NCT04870190). Clinical trial information: NCT03849768.