Aumolertinib (formerly almonertinib; HS-10296), a third-generation EGFR tyrosine kinase inhibitor (TKI), has demonstrated a significant improvement in progression-free survival (PFS) compared to placebo in patients with unresectable stage III non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R mutations. The findings come from an interim analysis of the phase 3 POLESTAR trial (NCT04951635), presented at the 2024 International Association for the Study of Lung Cancer World Conference on Lung Cancer. The study highlights aumolertinib as a potential novel treatment option for this patient population following chemoradiation therapy (CRT).
POLESTAR Trial Results
The POLESTAR trial, a randomized, double-blind, placebo-controlled, multicenter study, enrolled 147 patients across 43 sites in China. Patients were randomized 2:1 to receive 110 mg of aumolertinib once daily or placebo. The primary endpoint was BICR-assessed PFS per RECIST v1.1 criteria. Key secondary endpoints included overall survival (OS), overall response rate (ORR), and central nervous system (CNS) PFS.
At a median follow-up of 16.36 months in the aumolertinib arm (n = 92) and 13.93 months in the placebo arm (n = 50), aumolertinib reduced the risk of disease progression or death by 80% compared to placebo (HR, 0.200; 95% CI, 0.114-0.352; log-rank P < .0001). The median PFS was 30.4 months (95% CI, 17.2-not reached) with aumolertinib compared to 3.8 months (95% CI, 3.7-5.6) with placebo, according to blinded independent central review (BICR) assessment.
Investigator assessment yielded similar results, with a median PFS of 30.4 months (95% CI, 22.1-NR) for aumolertinib versus 3.8 months (95% CI, 3.7-5.6) for placebo (HR, 0.150; 95% CI, 0.080-0.284; log-rank P < .0001).
Additional Efficacy Data
Aumolertinib also demonstrated a significantly higher overall response rate (ORR) of 57% (95% CI, 46%-67%) compared to 22% (95% CI, 11%-34%) for placebo (OR, 4.58; 95% CI, 2.07-10.14; P < .0001). The disease control rates (DCRs) were 96% (95% CI, 92%-100%) and 74% (95% CI, 62%-86%), respectively (OR, 8.53; 95% CI, 2.54-28.66; P = .0001). The median duration of response (DOR) was 16.59 months (95% CI, 15.05-NR) in the aumolertinib arm versus 7.1 months (95% CI, 1.71-17.51) in the placebo arm (HR, 0.476; 95% CI, 0.168-1.349; P = .1557).
At a median follow-up of 16.6 months for the aumolertinib group and 14.9 months for the placebo group, overall survival (OS) data reached 9.8% maturity for the experimental arm and 6% maturity for the control arm. The median OS was not reached in either group.
The median CNS PFS was not reached (95% CI, NR-NR) in both arms (HR, 0.33; 95% CI, 0.12-0.92; P = .0270). The median time to death or distant metastases (TTDM) was not reached (95% CI, NR-NR) in the aumolertinib arm versus not reached (95% CI, 3.84-NR) in the placebo arm (HR, 0.21; 95% CI, 0.09-0.49; P < .0001).
Safety Profile
The safety profile of aumolertinib was generally favorable. Any-grade treatment-related adverse events (TRAEs) occurred in 84% of patients in the aumolertinib arm and 43.4% of patients in the placebo arm. The rates of grade 3 or higher TRAEs were 9.6% and 1.9%, respectively. Serious TRAEs were reported in 6.4% of patients in the experimental arm versus 1.9% of patients in the control arm. No TRAEs led to death in either arm.
The most common any-grade AEs reported in at least 10% of patients included increased blood creatinine phosphokinase levels (aumolertinib, 46%; placebo, 8%), radiation pneumonitis (45%; 30%), and decreased white blood cell count (31%; 11%).
"Interstitial lung disease [ILD] was not reported for aumolertinib, but it was reported in 1 patient for placebo [who experienced grade 3 ILD]," noted lead study author Xiangjiao Meng, MD, of Shandong Cancer Hospital and Institute at Shandong First Medical University in Jinan, China.
