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Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small Cell Lung Cancer
Jianxing He1, Masahiro Tsuboi2, Walter Weder3
1Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China State Key Laboratory of Respiratory Disease & National Clinical Research Centre for Respiratory Disease, Guangzhou, China.
Purpose:
Adjuvant osimertinib is the standard of care for patients with resected epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Neoadjuvant treatment could improve surgical and long-term outcomes.
Methods:
In this randomized, controlled, phase III study, patients with resectable, EGFR-mutated, stage II-IIIB NSCLC were randomly assigned (1:1:1) to receive neoadjuvant osimertinib (80 mg orally once daily for ≥9 weeks) plus platinum-based chemotherapy (once every 3 weeks for three cycles), osimertinib monotherapy (for ≥9 weeks), or placebo plus platinum-based chemotherapy (control), followed by surgical resection. Adjuvant osimertinib was offered to eligible patients after completion of surgery. The primary end point was major pathologic response (MPR) by blinded central pathology review. Event-free survival (EFS) was a secondary end point.
Results:
Overall, 358 patients were randomly assigned to receive osimertinib plus chemotherapy (121 patients), osimertinib monotherapy (117 patients), or placebo plus chemotherapy (120 patients). Osimertinib plus chemotherapy (MPR rate 26%) and osimertinib monotherapy (25%) demonstrated statistically significant improvement in the MPR rate versus placebo plus chemotherapy (2%), with corresponding odds ratios of 19.82 (95.002% CI, 4.60 to 85.33; P < .0001) and 19.28 (99.9% CI, 1.71 to 217.39; P < .0001), respectively. With 15% data maturity, the EFS rates at 12 months were 93%, 95%, and 83% with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. In the neoadjuvant period, grade ≥3 adverse events of any cause occurred in 36%, 13%, and 33% of patients with osimertinib plus chemotherapy, osimertinib monotherapy, and placebo plus chemotherapy, respectively. No new safety concerns were identified.
Conclusion:
Neoadjuvant osimertinib with or without chemotherapy demonstrated statistically significant improvement in the MPR rate over chemotherapy alone in patients with resectable, EGFR-mutated, stage II-IIIB NSCLC.
Insights
Neoadjuvant osimertinib, with or without chemotherapy, significantly improved major pathologic response rates in patients with resectable EGFR-mutated non-small cell lung cancer. This approach offers a promising alternative to standard adjuvant therapy.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Adjuvant osimertinib is standard for resected EGFR-mutated NSCLC.
- Neoadjuvant treatment may enhance surgical and long-term outcomes.
Purpose of the Study:
- To evaluate the efficacy of neoadjuvant osimertinib, alone or with chemotherapy, versus placebo plus chemotherapy in resectable EGFR-mutated NSCLC.
Main Methods:
- Phase III randomized controlled trial involving 358 patients with resectable, EGFR-mutated, stage II-IIIB NSCLC.
- Patients received neoadjuvant osimertinib plus chemotherapy, osimertinib monotherapy, or placebo plus chemotherapy for ≥9 weeks before surgery.
- Primary endpoint was major pathologic response (MPR); secondary endpoint was event-free survival (EFS).
Main Results:
- Neoadjuvant osimertinib plus chemotherapy (26% MPR) and osimertinib monotherapy (25% MPR) showed significant MPR improvement versus placebo plus chemotherapy (2%).
- 12-month EFS rates were 93% (osimertinib + chemo), 95% (osimertinib alone), and 83% (placebo + chemo).
- Grade ≥3 adverse events occurred in 36% (osimertinib + chemo), 13% (osimertinib alone), and 33% (placebo + chemo); no new safety concerns emerged.
Conclusions:
- Neoadjuvant osimertinib, with or without chemotherapy, significantly improves MPR rates in resectable EGFR-mutated NSCLC.
- This strategy represents a potential advancement over current standard care for this patient population.
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