Combination of Aumolertinib and Chemotherapy Enhances Survival Rates in NSCLC Patients

Recent findings from the ACROSS 2 Phase III clinical trial indicate that the combination of aumolertinib with platinum-pemetrexed chemotherapy significantly enhances progression-free survival (PFS) compared to aumolertinib alone in patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) who possess EGFR sensitizing mutations alongside tumor suppressor gene mutations.

The results were disclosed by a lead researcher from the National Cancer Center in China during the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC). Aumolertinib is recognized as an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) specifically designed for treating EGFR-mutated NSCLC.

Patients exhibiting EGFR concomitant mutations generally face unfavorable prognoses, and until now, there has been no established standard treatment regimen for this demographic. Prior studies have hinted that the efficacy of an EGFR-TKI may be improved when paired with chemotherapy rather than administered alone.

ACROSS 2 is noted as the first global, multicenter, open-label, randomized, controlled Phase III trial addressing the impact of this combination therapy. In this trial, patients with histologically confirmed stage IIIB-IV NSCLC, possessing EGFR sensitizing mutations along with tumor suppressor gene mutations and maintaining an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, were randomized in a 1:1 ratio. They either received aumolertinib at a daily dose of 110 mg combined with carboplatin (AUC=5) and pemetrexed (500 mg/m² every three weeks) or were treated with aumolertinib monotherapy until disease progression occurred. The trial also accounted for stratification factors such as the type of EGFR mutation (Ex19del/L858R) and the presence of central nervous system (CNS) metastases.

The primary objective of the trial was to evaluate progression-free survival, while secondary objectives included assessing the objective response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), and safety metrics. The median follow-up duration was reported as 25.3 months, revealing a median PFS of 19.78 months for the combination therapy group compared to 16.53 months for those receiving monotherapy, with a hazard ratio (HR) of 0.55 (95% CI: 0.339-0.910; p=0.0205).

The baseline characteristics were well balanced between the treatment cohorts, although overall survival data remain immature. Adverse events classified as treatment-emergent, reported at a rate of 20% or higher, included decreased white blood cell count, neutrophil count, and platelet count, as well as anemia, increased liver enzymes, elevated serum creatinine levels, nausea, constipation, and rash.

The addition of chemotherapy did not appear to alter the safety profile of aumolertinib, with no new safety signals identified during the trial. The lead researcher emphasized that this Phase III trial is the first to demonstrate a statistically significant progression-free survival benefit when aumolertinib is administered in conjunction with platinum-pemetrexed chemotherapy, while maintaining a manageable safety profile.