Adjuvant Aumolertinib Boosts DFS in Stage II-IIIB, EGFR-Mutated NSCLC

EGFR-Mutated NSCLC | Image Credit:
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The administration of aumolertinib (Ameile) in the adjuvant setting following complete tumor resection led to a significant improvement in disease-free survival (DFS) compared with placebo in patients with stage II to IIIB non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, according to data from the phase 3 ARTS trial (NCT04687241) presented at the 2025 AACR Annual Meeting.1

Findings showed that at a median follow-up of 27.6 months, patients treated with aumolertinib (n = 106) achieved a median DFS of that was not reached (NR; 95% CI, 29.1-not applicable [NA]) compared with 19.4 months (95% CI, 11.2-26.2) in patients given placebo (n = 104) per blinded independent central review (BICR; HR, 0.17; 95% CI, 0.09-0.29; P < .0001). The 24-month DFS rates were 88.2% for aumolertinib vs 40.6% for placebo.

“Aumolertinib was tolerable, suggesting this strategy is suitable for long-term administration as adjuvant therapy,” lead study author Ying Cheng, MD, said in a presentation of the data. “[Aumolertinib] offers a practice-changing option for this defined population.” Cheng is director of the Jilin Lung Cancer Diagnosis and Treatment Centre in Changchun, China.

Illustrating the ARTS Trial

The randomized, placebo-controlled, double-blind, multicenter trial evaluated aumolertinib, a third-generation, oral, irreversible EGFR TKI, which had previously displayed efficacy and safety in the treatment of patients with NSCLC harboring EGFR-sensitizing and T790M mutations.

The agent has been previously approved by China’s National Medical Products Administration in 3 different NSCLC indications:2

• for the second-line treatment of patients with locally advanced or metastatic NSCLC harboring an EGFR T790M mutation whose disease has progressed on or after an EGFR TKI;
• for the first-line treatment of adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations;
• and for the treatment of patients with locally advanced, unresectable, stage III NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations whose disease has not progressed following definitive platinum-based chemoradiotherapy.

During the presentation, Cheng explained that the high prevalence of EGFR mutations in the Asian NSCLC population, which ranges from approximately 30% to 50%, fueled the rationale behind the ARTS study.1

Investigators enrolled patients at least 18 years of age with stage II to IIIA or IIIB (T3N2M0) NSCLC who had EGFR 19 deletions or exon 21 L858R substitution mutations. Patients were required to have an R0 resection, be indicated for standard adjuvant therapy after surgery, and have an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to receive aumolertinib at 110 mg or placebo once daily. Treatment in both arms continued for up to 3 years or until disease recurrence or other discontinuation criteria were met.

Stratification factors included EGFR mutation status (exon 19 deletion vs exon 21 L858R substitution mutation) and tumor stage (II vs IIIA, N2-negative vs IIIA/B, N2-positive).

DFS per BICR assessment served as the trial’s primary end point. Secondary end points included investigator-assessed DFS; landmark DFS rates at 2, 3, and 5 years; overall survival (OS); 5-year OS rate; safety; and pharmacokinetics.

At baseline, the median age was 58 years (range, 30-75) in the aumolertinib arm (n = 107) vs 60 years (range, 38-77) in the placebo arm (n = 107). The majority of patients in both arms were female (aumolertinib arm, 55%; placebo arm, 57%), were non-smokers (72%; 70%), had an ECOG performance status of 1 (64%; 59%), had adenocarcinoma (100%; 96%), and received adjuvant chemotherapy (94%; 96%). Tumor staging at diagnosis comprised stage II (45%; 45%), IIIA (50%; 45%), and IIIB (5%; 8%).

In the experimental arm, 52% and 485 of patients harbored EGFR exon 19 deletions and exon 21 L858R substitution mutations, respectively. These respective rates were 49% and 51% in the control arm.

Additional Efficacy and Safety Data

An investigator assessment showed the median DFS was NR (95% CI, 29.1-NA) in the aumolertinib arm vs 22.1 months (95% CI, 13.9-27.8) in the placebo arm (HR, 0.17; 95% CI, 0.09-0.30; P < .0001). The 24-month DFS rates were 90.2% and 44.4%, respectively.

Per BICR assessment, the DFS benefit observed with aumolertinib was consistent across all predefined subgroups. Specifically regarding disease stage, the median DFS was NR (95% CI, 27.9-NA) in patients with stage II disease treated with aumolertinib (n = 48) compared with 27.8 months (95% CI, 11.5-NA) for those given placebo (n = 48; HR, 0.09; 95% CI, 0.03-0.31; P < .0001). In those with stage III disease, the median DFS was NR (95% CI, 29.1-NA) for aumolertinib (n = 58) vs 11.3 months (95% CI, 8.4-22.0) for placebo (n = 46; HR, 0.20; 95% CI, 0.10-0.38; P < .0001).

The median OS was NR (95% CI, NA-NA) in both arms with data at 2.8% (events, n = 3) maturity for the aumolertinib arm and 3.8% (events, n = 4) for the placebo arm. Censoring occurred for 103 and 100 patients in the experimental and control arms, respectively.

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 98.1% of patients in the aumolertinib group (n = 106) vs 94.4% of patients in the placebo group (n = 107). The rates of grade 3 or higher TEAEs were 27.4% and 21.5%, respectively. TEAEs did not lead to death in any patients in either arm.

In the aumolertinib arm, TEAEs led to treatment interruption, reduction, and discontinuation in 12.3%, 9.4%, and 0.9% of patients, respectively. These respective rates in the placebo arm were 17.8%, 1.9%, and 0%.

Any-grade treatment-related AEs (TRAEs) were observed in 93.4% of patients in the aumolertinib group compared with 75.7% of those in the placebo group. The respective rates of grade 3 or higher TRAEs were 13.2% and 7.5% of patients. Serious TRAEs occurred in 0.9% of patients in the aumolertinib group vs 2.8% of patients in the placebo group.

TRAEs led to treatment interruption, reduction, and discontinuation in 7.5%, 9.4%, and 0.9% of patients in the experimental arm, respectively. These respective rates were 7.5%, 1.9%, and 0% for the control arm.

The most common any-grade TEAEs of any cause reported in at least 15% of patients included increased creatine phosphokinase levels (aumolertinib arm, 60.4%; placebo arm, 14.0%), increased aspartate aminotransferase levels (28.3%; 19.6%), increased alanine aminotransferase levels (26.4%; 27.1%), cough (19.8%; 11.2%), COVID-19 (17.9%; 15.0%), rash (17.9%; 7.5%), pruritus (17.9%; 7.5%), diarrhea (17.0% 7.5%), pyrexia (16.0%; 4.7%), decreased white blood cell count (15.1%; 14.0%0, and upper respiratory tract infection (15.1%; 15.0%).

Disclosures: Cheng did not report any financial relationships.

References

1. Cheng Y, Zhang X, Wu L, et al. Aumolertinib as adjuvant therapy in patients with stage II-IIIB EGFR-mutated NSCLC after complete tumor resection: a randomized, double-blind, placebo-controlled, phase 3 trial (ARTS). Presented at: 2025 AACR Annual Meeting; April 25-30, 2025; Chicago, IL. Abstract CT126.
2. Hansoh Pharma's Ameile marketing application approved for third indication. News release. Hansoh Pharma. March 10, 2025. Accessed April 30, 2025. https://www.hspharm.com/news/news-detail-513292.htm