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Published on: November 22, 2021
Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell
Collin M Blakely1,2, Anatoly Urisman2,3, Matthew A Gubens1,2
1Department of Medicine, University of California, San Francisco, San Francisco, CA.
Purpose:
To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).
Patients And Methods:
This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.
Results:
A total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).
Conclusion:
Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.
Insights
Neoadjuvant osimertinib (a third-generation EGFR inhibitor) showed a 14.8% major pathological response rate in early-stage EGFR-mutated non-small cell lung cancer. The treatment was safe, with no surgical delays or increased unresectability.
Area of Science:
- Oncology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) with EGFR mutations often requires targeted therapy.
- Third-generation EGFR tyrosine kinase inhibitors (TKIs) offer new treatment avenues.
- Neoadjuvant therapy aims to reduce tumor burden before surgery.
Purpose of the Study:
- To evaluate the safety and efficacy of neoadjuvant osimertinib in patients with resectable EGFR-mutated NSCLC.
- To determine the major pathological response (MPR) rate as the primary endpoint.
- To assess secondary safety and efficacy outcomes and exploratory tumor genomic alterations.
Main Methods:
- A multi-institutional phase II clinical trial (NCT03433469) was conducted.
- Patients with resectable stage I-IIIA EGFR-mutated NSCLC received osimertinib 80 mg daily for up to two 28-day cycles.
- The primary endpoint was the MPR rate; secondary endpoints included safety, overall response rate (ORR), and disease-free survival (DFS).
Main Results:
- Twenty-seven patients were enrolled; 24 underwent surgery. The MPR rate was 14.8% (95% CI, 4.2 to 33.7), with no pathological complete responses observed.
- The ORR was 52%, and the median DFS was 40.9 months. One serious adverse event (3.7%) occurred.
- No patients experienced surgical delays or became unresectable due to adverse events. TP53 and RBM10 were common co-occurring alterations.
Conclusions:
- Neoadjuvant osimertinib did not meet the primary endpoint for MPR rate in surgically resectable EGFR-mutated NSCLC.
- The treatment demonstrated an acceptable safety profile, without compromising surgical eligibility or causing delays.
- Further research may explore optimizing neoadjuvant strategies for EGFR-mutated NSCLC.
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