Background
Phase II NAOS trial, N=35, single-arm, of neoadjuvant osimertinib in resectable EGFR-mutant stage II–IIIA NSCLC: 3 mo osimertinib prior to surgery.
Interventions and follow up
Treatment: Osimertinib 80 mg PO daily for 3 mo prior to surgery
Primary endpoint: Major pathologic response (MPR), ≤10% viable tumor
mFollow up: ~12 mo post-surgery
Primary endpoint: Major pathologic response (MPR), ≤10% viable tumor
mFollow up: ~12 mo post-surgery
Results
MPR rate: 14.8% (5 of 33 evaluable); did not meet predefined threshold
pCR: 0%
ORR: 52%
Surgery feasibility: 89% underwent resection; 11% unresectable progression at surgery
mDFS: 40.9 mo
pCR: 0%
ORR: 52%
Surgery feasibility: 89% underwent resection; 11% unresectable progression at surgery
mDFS: 40.9 mo
Adverse events
Overall: Mostly grade 1–2; no grade 3–4 toxicity from neoadjuvant osimertinib
Surgical: No perioperative mortality; 11% required surgery postponement for minor AEs
Surgical: No perioperative mortality; 11% required surgery postponement for minor AEs
Conclusions
Neoadjuvant osimertinib monotherapy produced low pathological response (MPR ~15%). Although safe and not compromising resection, the modest tumor kill indicates osimertinib alone is insufficient as neoadjuvant therapy; combination strategies are needed.
Key Limitations
Small single-arm phase II (N=35); did not meet MPR threshold; short follow-up; no randomized comparator.
Clinical Context
Adjuvant osimertinib (ADAURA) is FDA/EMA approved for resected EGFR-mutant NSCLC; neoadjuvant osimertinib is not established. NAOS supports adjuvant rather than neoadjuvant EGFR TKI use per ASCO/ESMO.