[Perioperative Safety Analysis of Preoperative Targeted Therapy in Patients with ALK-positive Non-small Cell Lung Cancer].

Abstract

Background: Perioperative management of locally advanced non-small cell lung cancer (NSCLC) remains a significant clinical challenge. Although anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have established a definitive role in the adjuvant setting for ALK-positive NSCLC, clinical evidence supporting their preoperative application remains scarce. Recent exploratory trials, such as the ALNEO study, indicated that preoperative ALK-TKIs therapy can achieve favorable major pathological response (MPR) rates; however, documented data regarding its perioperative safety remain limited. This study aims to evaluate the perioperative safety and feasibility of preoperative ALK-TKIs therapy through a retrospective, single-center analysis.

Methods: A retrospective review was conducted using the data of ALK-positive NSCLC patients recorded in the prospective database of Department I of Thoracic Surgery at Peking University Cancer Hospital from 2021 to 2024, who underwent surgical resection following preoperative ALK-TKIs therapy. Short-term efficacy, surgical outcomes, perioperative complications, and long-term survival data were systematically evaluated.

Results: Eleven patients were included, predominantly consisting of female non-smokers (9/11), and the pathological type for all patients was adenocarcinoma. Baseline clinical staging included stage IIIA (n=7), stage IIIB (n=3), and stage IV with oligometastasis (n=1). All patients received preoperative ALK-TKIs, with 4 receiving concurrent chemotherapy. The objective response rate (ORR) was 81.8%. All patients successfully underwent surgery via video- or robotic-assisted thoracoscopic surgery. The mean operative time was (122.0±62.3) min and the median intraoperative blood loss was 74.0 mL (range: 5.0-300.0 mL). The MPR and pathological complete response (pCR) rates were 45.5% (5/11) and 27.3% (3/11), respectively. All patients received postoperative adjuvant therapy, primarily targeted drugs. At a median follow-up of 30 months, no deaths occurred in the entire cohort; however, three patients experienced disease recurrence (one with intestinal and liver metastases, and two with brain metastases).

Conclusions: Preoperative ALK-TKIs therapy demonstrates favorable safety and feasibility in this small-sample cohort of ALK-positive NSCLC patients.