Aumolertinib Promising Maintenance Therapy in EGFR+ NSCLC

SAN DIEGO — Treatment with the estimated glomerular filtration rate (EGFR) tyrosine kinase inhibitor (TKI) aumolertinib after chemoradiation was associated significant improvement in progression-free survival compared with placebo in patients with unresectable stage III EGFR-mutant non–small cell lung cancer (NSCLC).

The preplanned interim analysis of the phase 3 POLESTAR study also indicated that aumolertinib has a manageable safety profile, suggesting that the EGFR TKI could become a novel maintenance treatment option for these patients, said Xiangjiao Meng, MD, with Shandong Cancer Hospital and Institute, Shandong First Medical University, China.

Consolidation therapy with durvalumab is the standard of care for patients who do not have disease progression following concurrent chemoradiation. However, the specific benefit of consolidation immunotherapy for patients with EGFR-mutant NSCLC remains unclear, said Meng, who reported the results here at the IASLC 2024 World Conference on Lung Cancer.

Aumolertinib, a third-generation EGFR TKI approved in China, has established efficacy in both first-line and second-line treatments of EGFR-mutant NSCLC.

The POLESTAR study enrolled 147 patients with locally advanced EGFR-mutant (Ex19del or L858R) unresectable stage III NSCLC who had not progressed during or following definitive chemoradiation. Patients had an ECOG performance status of 0 or 1.

Ninety-four of the study participants received aumolertinib (110 mg once daily) and 53 received matching placebo, beginning no more than 6 weeks after the last dose of chemoradiation.

The modified intention-to-treat set for efficacy assessment included 92 patients in the aumolertinib group and 50 in the placebo group, with patient characteristics “well-balanced,” Meng reported.

Median follow-up was 16.36 months in the aumolertinib group, and 13.93 months in the placebo group.

Aumolertinib maintenance therapy was associated with an 80% reduction in risk for disease progression. Median progression-free survival, determined by blinded independent central review, was 30.4 months in the aumolertinib group, compared with 3.8 months in the placebo group (hazard ratio [HR], 0.200; P < .0001). This survival benefit, favoring aumolertinib, was consistent across predefined subgroups.

The objective response rate was higher with aumolertinib than placebo (57% vs 22%; odds ratio [OR], 4.58; P < .0001), as was the disease control rate (96% vs 74%; OR, 8.53; P = .0001). Median duration of response was 16.59 months with aumolertinib vs 7.10 months with placebo (HR, 0.476; P = .1557).

The median follow-up for overall survival was 16.6 months for aumolertinib and 14.9 months for placebo. Median overall survival (9.8% maturity for aumolertinib and 6.0% maturity for placebo) was not reached in either group.

Aumolertinib after chemoradiation was “well tolerated,” with no new safety signals identified, Meng reported.

Most adverse events were less than grade 3. The most common adverse events with aumolertinib, of any grade, included an increase in blood creatine phosphokinase (46%), radiation pneumonitis (45%), decreased white blood cell count (31%), decreased platelet count (21%), increased aspartate aminotransferase levels (21%), upper respiratory tract infection (21%), cough (17%), decreased neutrophil count (15%), increased weight (14%), anemia (14%), diarrhea (13%), increased blood creatinine (12%), and rash (12%).

Interstitial lung disease was not reported in the aumolertinib group, but it was reported in one patient in the placebo group, who experienced grade 3 disease, Meng noted.

The Elephant in the Room

Discussant for the study, Fiona Hegi-Johnson, MBBS, PhD, radiation oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia, said this study provides “more evidence” that adjuvant TKIs after chemoradiotherapy improves progression-free survival in both trial and real-world settings.

However, the “elephant in the room is that we still have problems accessing mutation testing for all our patients,” Hegi-Johnson said.

According to the global biomarkers survey done by the IASLC this year, more than 40% of patients still start treatment without being tested.

“We need to advocate for increased access to mutation testing for all our patients,” Hegi-Johnson concluded.

The study was funded by Hansoh Pharmaceutical Group Co., Ltd. Meng and Hegi-Johnson have no relevant disclosures.