Aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, has demonstrated significant efficacy as maintenance therapy for patients with unresectable stage III non-small cell lung cancer (NSCLC) harboring EGFR mutations. The interim results of the phase III POLESTAR study, presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer, revealed a statistically and clinically significant improvement in progression-free survival compared to placebo in patients who received aumolertinib after chemoradiotherapy.
Progression-Free Survival Improvement
The POLESTAR study reported a median progression-free survival of 30.4 months with aumolertinib compared to 3.8 months with placebo (HR = 0.200, P < .0001). This represents an 80% reduction in the risk of disease progression or death. The 12-month progression-free survival rate was 76% with aumolertinib and 21% with placebo, respectively.
"These findings demonstrate aumolertinib as a novel treatment option for patients with unresectable stage III EGFR-mutated non-small cell lung cancer after chemoradiotherapy," said study author Xiangjiao Meng, PhD, of Shandong Cancer Hospital and Institute, Shandong First Medical University, in China. "The substantial improvement in progression-free survival compared to current standards of care represents a significant advancement in the management of this patient population."
Study Details and Patient Population
The POLESTAR study was a randomized, double-blind, placebo-controlled phase III trial conducted across 43 sites in China. The study enrolled 147 patients with unresectable stage III EGFR-mutated (exon 19 deletion or L858R) NSCLC who had not experienced disease progression after definitive chemoradiotherapy. Patients were randomly assigned in a 2:1 ratio to receive either aumolertinib or placebo until disease progression, unacceptable toxicity, or other discontinuation criteria were met.
The primary endpoint was progression-free survival as assessed by blinded independent central review. Secondary endpoints included overall survival, objective response rate, disease control rate, central nervous system (CNS) progression-free survival, time to distant metastasis, and safety.
Consistent Benefit Across Subgroups
The progression-free survival benefit favoring aumolertinib was consistent across all predefined subgroups. The objective response rate was also significantly higher in the aumolertinib group at 57%, compared with 22% in the placebo group. Although the median overall survival was not reached in either group at the time of this interim analysis, there were fewer instances of CNS lesions and distant metastases with aumolertinib vs placebo.
Safety Profile
Aumolertinib demonstrated a manageable safety profile with no new safety signals identified. The most common adverse event was an increase in blood creatinine phosphokinase. Radiation pneumonitis was reported in 45% of patients receiving aumolertinib vs 30% in the placebo group, with none being grade 3 or higher. The rate of adverse events leading to treatment discontinuation was low and similar between the two groups (2.1% with aumolertinib vs 1.9% with placebo).
Expert Commentary
Fiona Hegi-Johnson, MD, a radiation oncologist at the Peter MacCallum Cancer Centre in Victoria and Senior Research Fellow at the University of Melbourne, Australia, called the POLESTAR study results “impressive” but also highlighted several important considerations when interpreting the data. She noted key differences between the POLESTAR study and the LAURA study, including the study population, treatment protocols, and staging methods.
Dr. Hegi-Johnson underscored the importance of proper staging and treatment planning, particularly the role of PET scans, and emphasized the need to consider the entire course of treatment, including the quality of radiotherapy delivery. She also highlighted a significant challenge in the field: limited access to mutation testing.
Future Directions
Long-term follow-up data on overall survival and quality-of-life measures will be crucial in fully establishing the role of aumolertinib in this setting. Additionally, studies exploring potential combinations with other targeted therapies or immunotherapies may further optimize treatment strategies for patients with EGFR-mutated NSCLC.
"The POLESTAR study results are highly encouraging and suggest that aumolertinib could become a valuable addition to our treatment arsenal for stage III EGFR-mutated NSCLC," Dr. Meng concluded. "The significant progression-free survival improvement, coupled with a tolerable safety profile, positions aumolertinib as a promising maintenance therapy option for these patients."
