Effect and outcomes analysis of anlotinib in non-small cell lung cancer patients with liver metastasis: results from the ALTER 0303 phase 3 randomized clinical trial

Purpose Liver metastasis (LM) is common in non-small cell lung cancer (NSCLC), and always predicted worse outcomes with no effective therapy. We aimed to evaluate the effects and prognosis in LM patients treated with anlotinib. Methods The present study is a post hoc analysis based on a multicenter, double-blind, phase 3 randomized clinical trial which designed to evaluate the efficacy and safety of anlotinib in patients with advanced NSCLC. A total of 437 patients were enrolled in present study, and 78 patients with LM. Results Patients with LM showed a worse outcome compared to those without LM (PFS median, 2.6 vs 4.2 months), and OS (median, 5.6 vs 9.4 months, both P < 0.0001). The anlotinib was associated with longer PFS (median, 3.0 months) compared with placebo (median, 0.9 months), with a hazard ratio (HR) of 0.23 (95%CI, 0.12–0.42; P < 0.0001). Furthermore, OS was marginally significantly better in anlotinib group (median 6.6 months), compared with placebo (median 4.0 months), HR 0.61 (95%CI, 0.36–1.02; P = 0.055). Multivariate analysis confirmed normal peripheral blood LDH/TBiL level predicted better PFS and OS, lower ECOG score acted as independently prognostic factor for superior OS. Anlotinib was more associated with hand–foot syndrome (7.7% vs 0) and serum TSH level rise (7.7% vs 3.8%) and well tolerated, all AEs were no more than grade 3. Conclusion Patients with LM had a dismal prognosis, anlotinib could lead to a better PFS in pretreated NSCLC patients, which suggested anlotinib is a potential third-line or further therapy in these patients.