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Does neoadjuvant targeted therapy provide an opportunity for resectable EGFR-mutant lung cancer: a real-world
Chao Lv1, Yuanyuan Ma1, Qin Feng2
1Department of Thoracic Surgery II, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Background:
Although neoadjuvant chemotherapy could improve survival outcome in resectable non-small cell lung cancer (NSCLC), the efficacy of neoadjuvant targeted therapy is still unclear.
Methods:
We retrospectively reviewed clinical records of stage I-IIIA lung adenocarcinoma patients treated with neoadjuvant targeted therapy or chemotherapy prior to surgery. The collected data were compared between the two groups. Tumor samples were collected and analyzed by sequencing to explore the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms.
Results:
A total of 134 patients were enrolled; of these, 119 (88.8%) had clinical stage II-IIIA disease. Radiographic response rate was significantly higher with neoadjuvant targeted therapy than with chemotherapy among patients harboring EGFR mutation [objective response rate (ORR): 55.8% vs. 32.6%; P=0.030]. EGFR exon 19 deletion achieved better tumor response than those with exon 21 L858R mutation (ORR: 70.0% vs. 40.0%; P=0.057). Postoperative complications, operation time, drainage volume, and postoperative hospital length of stay were comparable between two groups. There was no difference on disease free survival (DFS) between patients receiving neoadjuvant targeted therapy and chemotherapy (P=0.871), but those who continued long-term adjuvant targeted therapy had significantly longer DFS than those only treated with adjuvant chemotherapy postoperatively (P=0.011). A series of potential molecular mechanisms of EGFR-TKI primary resistance were detected; these included BIM deletion polymorphisms, EGFR T790M mutation, and PTEN, TSC1, PIK3CA, or STAT3 mutations. Patients who presented stable disease (SD) response after TKI therapy had significantly lower EGFR mutation abundance than PR response (P=0.032).
Conclusions:
Neoadjuvant EGFR-TKI appears to be more effective than conventional chemotherapy for EGFR-mutant NSCLC patients. This study provides evidence that needs to be investigated further in randomized controlled trials (RCT).
Insights
Neoadjuvant targeted therapy shows higher response rates than chemotherapy in EGFR-mutant non-small cell lung cancer (NSCLC) patients. Continued targeted therapy post-surgery improves disease-free survival, warranting further randomized trials.
Area of Science:
- Oncology
- Medical Research
Background:
- Neoadjuvant chemotherapy improves survival in resectable non-small cell lung cancer (NSCLC).
- The effectiveness of neoadjuvant targeted therapy in NSCLC remains unclear.
Purpose of the Study:
- To compare the efficacy of neoadjuvant targeted therapy versus chemotherapy in lung adenocarcinoma patients.
- To investigate epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms.
Main Methods:
- Retrospective review of stage I-IIIA lung adenocarcinoma patients undergoing neoadjuvant therapy before surgery.
- Comparison of clinical data between targeted therapy and chemotherapy groups.
- Tumor sample sequencing to identify EGFR-TKI resistance mechanisms.
Main Results:
- Neoadjuvant targeted therapy demonstrated a significantly higher objective response rate (ORR) than chemotherapy in EGFR-mutant NSCLC (55.8% vs. 32.6%).
- EGFR exon 19 deletion showed better tumor response than exon 21 L858R mutation.
- Long-term adjuvant targeted therapy significantly improved disease-free survival compared to adjuvant chemotherapy (P=0.011).
- Identified potential EGFR-TKI resistance mechanisms including BIM deletion, EGFR T790M, PTEN, TSC1, PIK3CA, and STAT3 mutations.
Conclusions:
- Neoadjuvant EGFR-TKI is more effective than chemotherapy in EGFR-mutant NSCLC patients.
- Further investigation in randomized controlled trials (RCTs) is recommended.
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