Evaluation of the efficacy and safety of anlotinib in postoperative non-pCR non-small cell lung cancer.

Abstract

e20005 Background: Several phase III studies have confirmed the efficacy and safety of neoadjuvant immunochemotherapy for resectable non-small cell lung cancer (NSCLC). However, the pathological complete response (pCR) rate remains around 17.2-40.7%, with limited overall benefit for patients. Subgroup analyses have shown that patients who do not achieve pCR (non-pCR) after neoadjuvant immunochemotherapy have significantly worse event-free survival (EFS) compared to pCR patients. Their EFS is similar to that of chemotherapy-only group non-pCR patients, indicating that non-pCR patients benefit less from neoadjuvant immunochemotherapy. This group accounts for 70-80% of patients, highlighting the need for new clinical studies to explore and improve outcomes in this population. Anlotinib, a multi-target small-molecule tyrosine kinase inhibitor that can synergistically enhance immune therapy effectiveness. Methods: Patients with stage IB-IIIB NSCLC who underwent R0 resection and were confirmed as non-pCR after completing neoadjuvant immunochemotherapy were included. These patients received 1 year of anlotinib combined with immune adjuvant therapy. The primary endpoint of the study was disease-free survival (DFS). Secondary endpoints included overall survival (OS), DFS rates at 12/24 months, OS rates at 2/3 years, and safety. Exploratory analysis focused on the relationship between ctDNA status in peripheral blood before and after treatment and the efficacy of anlotinib adjuvant therapy. Results: From October 2023 to January 2025, 81 patients were enrolled, with 19 (23.5%) undergoing surgical resection after neoadjuvant immunochemotherapy. Among them, 13 (68.4%) were non-pCR patients, and 8 (61.5%) received anlotinib combined with immunotherapy as adjuvant treatment. The safety profile was consistent with the known safety profile of anlotinib. The incidence of grade 3 adverse events was 37.5%, with no grade 4 or higher adverse events. 25% of patients had their medication temporarily suspended or dosages adjusted due to adverse events, and 37.5% of patients discontinued the medication due to adverse events. No fatal adverse events were reported. KEGG pathway analysis revealed significant differential genes between pCR and non-pCR patients, primarily involved in sulfation modification and glycosaminoglycan biosynthesis—heparin/heparan sulfate pathway. The ctDNA positivity rate before neoadjuvant treatment was 93.3% (14/15), after treatment it was 14.3% (2/14), and post-surgery ctDNA was negative in all patients (0/5). One patient had a recurrence of ctDNA positivity during adjuvant treatment, but it turned negative as the treatment continued. Conclusions: Anlotinib adjuvant therapy did not show concerning safety data and holds potential for benefiting resectable non-pCR NSCLC patients after neoadjuvant treatment.