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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Outcomes with neoadjuvant osimertinib and/or chemotherapy in patients with EGFR-mutant resectable non-small cell lung
Prashasti Agrawal1, Julia Rotow2, Gaetano Rocco3
1Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA; Weill Cornell Medical College, 525 East 68th Street, New York, NY 10065, USA.
Background:
EGFR-inhibitors are currently not approved for neoadjuvant treatment of resectable EGFR-mutant non-small cell lung cancers (NSCLC). We report a real-world multi-institutional analysis of surgical and pathologic outcomes in patients with resectable EGFR-mutant NSCLC treated with neoadjuvant therapies.
Methods:
We identified patients with clinical stage II-IIIB NSCLC with sensitizing EGFR mutations who received neoadjuvant osimertinib and/or platinum-based doublet chemotherapy with intent for definitive surgical resection. Clinicopathologic characteristics and treatment outcomes were annotated. Event-free survival (EFS) was defined from the start of neoadjuvant treatment.
Results:
We identified 51 patients who received neoadjuvant osimertinib (N = 23, 45 %), chemotherapy alone (N = 18, 35 %), or osimertinib and chemotherapy (N = 10, 20 %). R0 resection rates were 91 % with osimertinib, 72 % with chemotherapy, and 90 % with osimertinib and chemotherapy. Rates of pathologic complete response were 17 % with osimertinib, 0 % with chemotherapy, and 0 % with osimertinib and chemotherapy. Rates of major pathologic response were 44 % with osimertinib, 0 % with chemotherapy, and 10 % with osimertinib and chemotherapy. Pathologic tumor downstaging occurred in 48 % with osimertinib, 44 % with chemotherapy, and 40 % with osimertinib and chemotherapy; pathologic lymph node downstaging occurred in 35 % with osimertinib, 28 % with chemotherapy, and 40 % with osimertinib and chemotherapy. Median follow up time was 19 months. Median EFS was 61 months with osimertinib, 32 months with chemotherapy, and 20 months with osimertinib and chemotherapy.
Conclusions:
Pathologic complete responses and major pathologic responses were only observed in patients with EGFR-mutant NSCLC treated with osimertinib. EGFR-inhibitors may play an important role in the preoperative management of EGFR-mutant lung cancer.
Insights
Neoadjuvant osimertinib shows promise for resectable EGFR-mutant non-small cell lung cancer (NSCLC), leading to higher response rates and improved event-free survival compared to chemotherapy alone. These findings suggest a significant role for EGFR inhibitors in preoperative lung cancer management.
Area of Science:
- Oncology
- Thoracic Surgery
- Pharmacology
Background:
- Epidermal Growth Factor Receptor (EGFR) inhibitors are not currently approved for neoadjuvant treatment in resectable EGFR-mutant non-small cell lung cancer (NSCLC).
- Real-world data on neoadjuvant therapies for this patient population are limited.
- Surgical and pathological outcomes require further investigation.
Purpose of the Study:
- To analyze surgical and pathological outcomes in patients with resectable EGFR-mutant NSCLC treated with neoadjuvant therapies.
- To compare the efficacy of neoadjuvant osimertinib, chemotherapy, and combination therapy.
- To evaluate the role of EGFR inhibitors in the preoperative management of NSCLC.
Main Methods:
- Retrospective analysis of 51 patients with clinical stage II-IIIB NSCLC and sensitizing EGFR mutations.
- Patients received neoadjuvant osimertinib, platinum-based doublet chemotherapy, or both.
- Clinicopathological characteristics and treatment outcomes, including event-free survival (EFS), were annotated.
Main Results:
- R0 resection rates were highest with osimertinib (91%) and combination therapy (90%) compared to chemotherapy alone (72%).
- Pathologic complete response (17%) and major pathologic response (44%) were observed only with osimertinib.
- Median EFS was longest with osimertinib (61 months) compared to chemotherapy (32 months) and combination therapy (20 months).
Conclusions:
- Neoadjuvant osimertinib monotherapy demonstrated superior pathologic response rates and event-free survival in resectable EGFR-mutant NSCLC.
- EGFR inhibitors, such as osimertinib, may be a valuable component of neoadjuvant treatment strategies for EGFR-mutant lung cancer.
- Further prospective studies are warranted to confirm these findings.
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