Improved progression-free survival with aumolertinib maintenance in stage III NSCLC

In the phase III POLESTAR study, the epidermal growth factor receptor tyrosine kinase inhibitor aumolertinib demonstrated improved progression-free survival compared to placebo as maintenance treatment after chemoradiotherapy in stage III, unresectable EGFR- mutated non-small cell lung cancer.

Consolidation therapy with durvalumab is established as the standard-of-care for patients who do not experience disease progression following concurrent chemoradiotherapy (cCRT). However, the specific benefit of consolidation immunotherapy for patients with EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) remains uncertain. Aumolertinib, a third-generation EGFR TKI, has demonstrated established efficacy in both first-line and second-line treatments of EGFRm NSCLC and has received regulatory approval in China. The double-blind, placebo-controlled, phase III POLESTAR study aims to investigate the use of aumolertinib after chemoradiotherapy (CRT) in stage III, unresectable EGFRm NSCLC.

Study design

Adult patients with EGFRm (Ex19del or L858R) locally advanced or unresectable stage III NSCLC who had not progressed after cCRT/sequential CRT (sCRT) were randomised 2:1 to receive aumolertinib (110 mg qd po, N= 94) or placebo (N= 53) until disease progression per RECIST v1.1, toxicity or other discontinuation criteria. The primary endpoint is progression-free survival (PFS) assessed by blinded independent central review (BICR). Secondary endpoints include overall survival, other efficacy endpoints and safety. Tumours were assessed every 8 weeks to week 48, then every 12 weeks until progression. Crossover is allowed for patients in the placebo arm.

Results

Median follow-up was 16.36 months for aumolertinib and 13.93 months for placebo. The modified intention-to-treat (mITT) set for efficacy assessment included 92 patients in the aumolertinib arm and 50 patients in placebo arm, with patient characteristics being well-balanced. Patients in the aumolertinib arm had a longer PFS than patients randomised to the placebo group. Median PFS by BICR was 30.4 months for patients treated with aumolertinib compared with 3.8 months for patients in the placebo group (HR[95%CI]: 0.200[0.114-0.352],  p< 0.0001). Investigator-assessed PFS results were consistent with the findings of the BICR and the PFS benefit favouring aumolertinib was consistent across predefined subgroups. Furthermore, objective response rate (57% vs. 22%, p< 0.0001) and disease control rate (96% vs. 74%, p= 0.0001) were higher with aumolertinib than with placebo and the median duration of response was longer with aumolertinib than with placebo (16.59 vs. 7.10 months, p= 0.1557). After a median follow-up for OS of 16.6 months for aumolertinib and 14.9 months for placebo, median OS (9.8% maturity for aumolertinib and 6.0% maturity for placebo) was not reached in either group.

The most common adverse event (AE) for aumolertinib was increased blood creatine phosphokinase. The majority of AEs were grade <3. Radiation pneumonitis was reported in 45% vs. 30% for aumolertinib vs. placebo, with none being grade ≥3. There were no cases of interstitial lung disease in the aumolertinib group, and one event in the placebo group.

Conclusion

In the POLESTAR study, aumolertinib exhibited a statistically and clinically significant improvement in PFS compared to the placebo group in patients with unresectable stage III EGFR-mutated NSCLC following definitive chemoradiotherapy. The overall safety profile of aumolertinib after chemoradiotherapy was well tolerated and manageable, with no new safety signals identified. These findings demonstrate aumolertinib as a novel treatment option for patients with unresectable stage III EGFRm NSCLC after CRT.

Reference

Meng X, et al. Aumolertinib after Chemoradiotherapy in Unresectable Stage III Non-Small-Cell Lung Cancer with EGFR Mutation: Interim Analysis of the Phase III POLESTAR Study. Presented at WCLC 2024; Abstract 774.