Abstract 5964: Real world efficacy and safety of anlotinib in solid tumors previously treated with immune checkpoint inhibitors

Abstract Backgrouds Immune checkpoint inhibitors (ICIs) resistance of solid tumors is common and subsequent treatment options offer limited clinical benefit. Anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI) for tumor angiogenesis and proliferative signaling. Recent preclinical studies have suggested that anlotinib can reverse resistance to ICIs by modulating the immunosuppressive tumor microenvironment (TME). The current real-world study aimed to investigate the efficacy and safety of anlotinib for solid tumors in Chinese patients who have previously accepted ICIs alone or combined treatments. Methods Data of patients diagnosed with solid tumors and previously accepted ICIs were collected retrospectively from six medical sites in China between Jan 2018 and May 2024. Patients were divided into two groups according to the subsequent treatments: anlotinib alone or combined therapy; other treatmental methods not including anti-angiogenic TKIs. Propensity score matching (PSM) based on age, gender, TNM staging, and lines of therapy was used. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Adverse Events were graded by CTCAE v4.03. Results A total of 911 patients were enrolled, including 539 (59.2%) non-small cell lung cancer (NSCLC), 210 (23.1%) hepatocellular carcinoma, 65 (7.1%) esophageal cancer, 59 (6.5%) gastric cancer, 30 (3.3%) cervical cancer, and 8 (0.9%) endometrial cancer. The median age was 58.0 years (range 51.5-66.0), 74.6% were male, 63.6% were stage IV, and 63.9% had received only first-line treatment. In the total population, after 2:1 PSM, there were 431 and 216 patients in the anlotinib and other treatments group, respectively. The PFS was significantly longer in the anlotinib group than in other treatments group (median, 7.9 months vs 6.2 months; HR 0.79, 95% CI 0.62-1.00; P=0.039). The objective response rate (ORR) was 9.5% (41/431) with anlotinib and 11.6% (25/216) with other treatments. We further compared the outcomes of anlotinib combination therapy with other treatments, and results showed that after 2:1 PSM, the median PFS with anlotinib combination (n=404) was 7.9 months versus 6.1 months with other treatments (n=203) (HR 0.72, 95% CI 0.57-0.91; P=0.002). The ORR was 10.1% (41/404) with anlotinib combination and 11.8% (24/203) with other treatments. Of the 431 patients treated with anlotinib, the most common adverse events (≥5% of patients) were allergy (9.7%), gastrointestinal events (8.6%), bleeding (7.7%), and hand-foot syndrome (5.6%). Conclusion Our study demonstrated the favorable anti-tumor activity and manageable toxicity of anlotinib treatment in solid tumors previously treated with ICIs, and anlotinib combination may provide more benefit. To our knowledge, this study represents the largest real-world clinical data of anlotinib therapy for solid tumors. Citation Format: Changzhen Shang, Xuan Luo, Jinyi Zhong, Yajin Chen. Real world efficacy and safety of anlotinib in solid tumors previously treated with immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5964.