Comprehensive study of neoadjuvant targeted therapy for resectable non-small cell lung cancer

Approximately 30-70% percent of patients with non-small cell lung cancer (NSCLC) still relapse after receiving complete resection and even suffer distant metastasis. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have gradually replaced chemotherapy to become the first-line postoperative NSCLC treatment because they can effectively inhibit the postoperative recurrence of lung cancer. However, the clinical efficacy of neoadjuvant EGFR-TKIs in EGFR mutant NSCLC patients is still unclear. The purpose of this study was to evaluate their clinical efficacy and to further explore factors affecting recurrence in such patients.

EGFR-mutated patients receiving neoadjuvant EGFR-TKI treatment in our hospital from July 2016 to September 2020 were retrospectively included. These patients underwent radical tumor resection after treatment. The primary endpoint was the objective response rate (ORR). The secondary endpoints were the major pathological response (MPR), disease-free survival (DFS), and overall survival (OS).

A total of 42 patients who met the inclusion criteria were included in this study. The ORR was 47.6% (20/42), and the MPR was 23.8% (10/42). The average follow-up time was 23.7 months. As of the final follow-up date, 18 (42.9%, 18/42) patients had experienced tumor recurrence. Of these, there were 11 (61.1%) cases of local recurrence and 7 (38.9%) cases of distant metastasis, including 5 bone metastases and 2 brain metastases. Multivariate Cox regression results showed that the high-risk subtype [P=0.012, hazard ratio (HR) =24.560; 95% confidence interval (CI), 2.016-299.227] was a risk factor for postoperative recurrence. Patients with a high-risk subtype (solid or micropapillary subtype) had significantly worse recurrence-free survival (RFS, log-rank P=0.032). Although patients with pathological remission had a similar RFS as patients who did not achieve pathological remission (log-rank P=0.069), the patients without pathological remission showed a tendency toward a worse prognosis.

Neoadjuvant EGFR-TKIs had good effects on EGFR-mutant NSCLC patients at different stages, especially those with MPR. Patients with high-risk subtypes (solid or micropapillary) should be closely followed up after surgery because of the high risk of recurrence.