Aumolertinib as adjuvant therapy in resected EGFR-mutated non-small-cell lung cancer (ARTS): a double-blind, multicentre, randomised, controlled, phase 3 trial

Patients with resectable non-small-cell lung cancer (NSCLC), particularly those with EGFR mutations, face a high risk of recurrence and mortality post-surgery. Aumolertinib, a third-generation EGFR tyrosine-kinase inhibitor, is approved in China for adjuvant treatment in patients with NSCLC harbouring EGFR with an exon 19 deletion (ex19del) or exon 21 substitution (Leu858Arg) mutation. The ARTS study aimed to evaluate the efficacy and safety of adjuvant therapy with aumolertinib in patients with stage II-IIIB EGFR-mutated NSCLC.

This double-blind, multicentre, randomised, controlled, phase 3 trial enrolled patients from 48 hospitals in mainland China. Eligible patients were 18 years or older with stage II-IIIB NSCLC, had undergone a complete resection followed by standard adjuvant therapy, and had an EGFR ex19del or Leu858Arg mutation and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were stratified by EGFR mutation status and tumour stage and were randomly assigned (1:1) to receive aumolertinib 110 mg or placebo orally, once daily for 3 years or until disease recurrence or other discontinuation criteria were met. Patients were randomly allocated to groups using an interactive web response system; the double‑dummy technique masked patients, investigators, and assessors. The primary endpoint was disease-free survival in the modified intention-to treat (mITT) population (ie, all patients with stage II-IIIB NSCLC harbouring EGFR mutations who had undergone complete tumour resection and standard adjuvant therapy), assessed by blinded independent central review (BICR). Safety was assessed in all patients who received at least one dose of study treatment. Although the study is ongoing, with some patients remaining in follow-up, this analysis represents the protocol-specified primary analysis. This study is registered with ClinicalTrials.gov (NCT04687241).

Between April 30, 2021, and May 17, 2022, 399 individuals were screened for study eligibility; of these, 214 patients were randomly assigned to receive aumolertinib or placebo (107 in each group). 120 (56%) patients were female, 94 (44%) were male, median age was 59 years (IQR 54-66), and all patients were Chinese. 204 (95%) of 214 patients had received prior adjuvant chemotherapy. One patient in the aumolertinib group and three patients in the placebo group had stage I disease; therefore, 106 patients in the aumolertinib group and 104 in the placebo group were included in the mITT (primary analysis) population. As of the data cutoff date (April 15, 2024), the median duration of follow-up was 27·56 months (IQR 22·18-27·70) in the aumolertinib group and 27·63 months (22·18-27·79) in the placebo group. The BICR-assessed disease-free survival was significantly improved in the aumolertinib group compared with the placebo group, with an HR of 0·17 (95% CI 0·09-0·29, p<0·0001). The median disease-free survival per BICR in the aumolertinib group was not reached (95% CI 29·14 to not applicable), whereas it was 19·42 months (11·24-26·22) in the placebo group. The most common grade 3-4 adverse events in the aumolertinib group versus the placebo group were increased blood creatine phosphokinase (seven [7%] vs none), prolonged electrocardiogram QT interval (three [3%] vs three [3%]), hypertension (one [1%] vs five [5%]), and pneumonia (two [2%] vs three [3%]). Treatment-related serious adverse events occurred in one (1%) patient receiving aumolertinib and three (3%) patients receiving placebo. No treatment-related deaths occurred and no new safety signals were identified for aumolertinib.

Aumolertinib showed substantial clinical benefits as adjuvant therapy in Chinese patients with stage II-IIIB EGFR-mutated NSCLC. The manageable safety profile of aumolertinib supports its suitability in the adjuvant setting.

Hansoh Pharmaceutical Group.

For the Chinese translation of the abstract see Supplementary Materials section.