NeoADAURA Insights: Evaluating Neoadjuvant Osimertinib With or Without Chemotherapy for Resectable EGFR-mutated NSCLC

Neoadjuvant osimertinib with or without chemotherapy “should be considered” for treating patients with resectable EGFR-mutated non–small cell lung cancer (NSCLC) in stages II-IIIB, according to results of the NeoADAURA study.

Jamie Chaft, MD, of the Memorial Sloan Kettering Cancer Center, and colleagues conducted the study to compare outcomes in EGFR-mutated, resectable NSCLC when patients were treated with neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone.

Xiuning Le, MD, PhD, of the MD Anderson Cancer Center, shared her thoughts on the study findings with Lung Cancers Today during the ASCO Annual Meeting.

It was important to conduct the study to expand on research performed in the phase 3 ADAURA study, which established adjuvant osimertinib as the standard of care for EGFR-mutated, resected NSCLC in stages IB-IIIA. The researchers noted that neoadjuvant treatment for the disease “may improve surgical and long-term outcomes.”

The phase 3 randomized controlled study identified eligible patients as individuals aged 18 years and older with EGFR-mutated, resectable NSCLC in stages II-IIIB with exon 19 deletions or L858R mutations. Patients were stratified by disease stage, race and ethnicity, and mutation type.

Eligible participants were randomized 1:1:1 to receive the following.

1. Neoadjuvant osimertinib (80 mg) once daily for 9 weeks or more plus three cycles of chemotherapy (cisplatin or carboplatin plus pemetrexed) every 3 weeks
2. Osimertinib monotherapy (80 mg) once daily for 9 weeks or more
3. Placebo once daily plus three cycles of chemotherapy (cisplatin or carboplatin plus pemetrexed) every 3 weeks

The cohorts receiving osimertinib or placebo plus chemotherapy were classified as double blind, and the osimertinib monotherapy cohort was classified as open label, sponsor blind. In addition, adjuvant osimertinib was offered to all patients who completed surgery.

The primary end point of the study was major pathologic response by blinded central pathology review and the secondary end points included pathologic complete response, event-free survival, and safety. The cutoff for gathering data for all cohorts was October 15, 2024.

A total of 358 patients were included in the study, with 121 patients receiving osimertinib plus chemotherapy, 117 patients receiving osimertinib alone, and 120 patients receiving placebo plus chemotherapy. The investigators explained that after receiving neoadjuvant treatment, 92% of patients in the osimertinib plus chemotherapy arm underwent surgery, as well as 97% in the osimertinib monotherapy arm and 89% in the placebo plus chemotherapy arm.

The major pathologic response rate in the osimertinib plus chemotherapy group was 26% versus 25% with osimertinib alone. Both groups showed statistically significant improvement in major pathologic response compared with the placebo plus chemotherapy group (2%). Furthermore, interim event-free survival “trended in favor” of both osimertinib groups versus the placebo group.

The researchers also highlighted adverse event data and reported that, in the neoadjuvant period, grade 3 or higher all-cause adverse events were observed in 36% of the osimertinib plus chemotherapy group, 13% of the osimertinib alone group, and 33% of the placebo group. Among grade 3 or higher adverse events “leading to the discontinuation of any Tx  [treatment],” the rates were 9%, 3%, and 5% for the three groups, respectively.

In reflecting on the results, the investigators highlighted that neoadjuvant osimertinib with or without chemotherapy showed statistically significant improvement in the rate of major pathologic response over chemotherapy alone. They also noted that event-free survival data trended in favor of both osimertinib arms.