At ASCO 2025, data from the Phase III NeoADAURA trial was presented involving neoadjuvant TAGRISSO as a single agent or in combination with chemotherapy in patients with resectable EGFR-mutated NSCLC.

In the study, patients treated with TAGRISSO plus chemotherapy showed a MPR rate of 26%, while those receiving TAGRISSO alone had an MPR rate of 25%. This was significantly higher than the 2% MPR rate observed in the placebo plus chemotherapy group. Pathological Complete Response (pCR) rates were 4% for the combination group, 9% for the monotherapy group, and 0% for the control group. Importantly, the MPR advantage with TAGRISSO-based treatments was consistent across all predefined subgroups. Compared to the chemotherapy-only arm, the odds of achieving MPR were markedly higher in the combination and monotherapy arms. Additionally, interim analysis of Event-free Survival (EFS), with 15% maturity, showed promising trends. TAGRISSO plus chemotherapy reduced the risk of events by 50%, while TAGRISSO monotherapy showed a hazard ratio of 0.73. At 12 months, EFS rates were 95% for TAGRISSO monotherapy, 93% for the combination group, and 83% for the placebo plus chemotherapy group. Median follow-up times were 14.3 months for both combination and control groups, and 18.3 months for the monotherapy group.

During the neoadjuvant phase, Grade ≥3 adverse events from any cause were reported in 36% of patients receiving osimertinib plus chemotherapy, 13% with osimertinib alone, and 33% with placebo plus chemotherapy. No new safety signals emerged.

KOL insights

“The interim EFS results trend favorably for each of the osimertinib-containing arms compared with chemotherapy alone and fewer patients with an MPR had an EFS event compared with patients without an MPR. Over 50% of patients with baseline N2 disease were downstaged at surgery contrasted to 21% with chemotherapy and the safety findings were consistent with the known profiles of the drugs.” – Expert Opinion

“When neoadjuvant treatment is recommended, osimertinib should be considered as part of that treatment for patients with EGFR-mutated NSCLC.” – Expert Opinion

Conclusion

NSCLC, which accounts for around 85% of all lung cancer cases. While no neoadjuvant targeted therapies are currently approved for EGFR-mutant NSCLC, research is ongoing. The treatment of EGFR-mutant NSCLC has been transformed by the development of targeted therapies in the last two decades; however, choosing the best therapy after EGFR TKIs fail is still a challenge.

Adjuvant TAGRISSO, a third-generation EGFR tyrosine kinase inhibitor, is the current standard of care for patients with resected stages 1B-3A EGFR-mutated NSCLC. If TAGRISSO gains approval for the neoadjuvant setting, AstraZeneca would become the sole company with approvals across all treatment lines.