Dr Blakely on the Rationale for Investigating Neoadjuvant Osimertinib in EGFR-Mutated NSCLC

Collin Blakely, MD, PhD, assistant clinical professor, Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco (UCSF), UCSF Health, discusses a phase 2 trial evaluating the use of neoadjuvant osimertinib (Tagrisso) in patients with surgically resectable EGFR-mutated non-small cell lung cancer (NSCLC), findings from which were presented at the 2023 ASCO Annual Meeting.

EGFR inhibitors are effective in the metastatic setting for treating patients with EGFR-mutated lung cancer, which occurs in approximately 15% to 20% of lung adenocarcinoma cases, Blakely begins, adding that trials such as the phase 3 ADAURA trial (NCT02511106) have shown that adjuvant treatments also improve disease-free survival compared with placebo. The rationale for conducting further research into this topic is for investigators to best understand the possibility of moving EGFR inhibitors earlier in the treatment course, prior to surgery, Blakely explains.

Trials such as the phase 3 KEYNOTE-671 study (NCT03425643) have shown that neoadjuvant treatments for patients with NSCLC, specifically chemotherapy in combination with immunotherapy, generate event-free survival, major pathological response, and pathological complete response improvements compared with placebo. However, immunotherapy cannot be used in EGFR-mutated lung cancer because of its toxicity profile and lack of efficacy in this population, Blakely emphasizes. Therefore, investigators aimed to evaluate neoadjuvant treatment with osimertinib in patients with surgically resectable EGFR-mutated lung cancer, specifically including patients with EGFR L858R– or exon 19 deletion–positive disease, he notes.

The primary end point of this study was major pathological response, which is now a well-accepted end point in a surgical neoadjuvant study, he expands. Major pathological response was defined as less than 10% viable cancer cells seen by the pathologist at surgery. Other studies have shown potential correlations between major pathological response and overall survival. Although this end point hasn't been thoroughly studied, it is a surrogate end point that many investigators are using in neoadjuvant trials, Blakely explains.

In this trial, the investigators hypothesized that osimertinib would elicit a high major pathological response rate, with the goal of a 50% major pathological response rate, he continues. However, in the 27 patients included in the trial, the major pathological response rate was 15%, Blakely concludes.