Anlotinib plus docetaxel in advanced NSCLC progressing on immunotherapy: A pooled analysis of two randomized trials.

8062 Background: This analysis aimed to evaluate outcomes of anlotinib plus docetaxel versus docetaxel alone in patients with advanced non-small cell lung cancer (NSCLC) after progression on immune-checkpoint inhibitors (ICIs) using the pooled data from two randomized trials (ALTER-L016; ALTER-L018). Methods: Eligible patients for this pooled analysis were aged 18-75 years and had EGFR/ALK/ROS1 wild-type advanced NSCLC progressing after first-line ICIs therapy. Patients were randomly assigned to receive anlotinib (10 mg [L016] or 12 mg [L018] once daily on days 1-14) plus docetaxel (60 mg/m 2 [L016] or 75 mg/m 2 [L018], on day 1 every 3 weeks) or docetaxel alone. The primary endpoint was progression-free survival (PFS). Second endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Total of 71 patients (L016, n = 39; L018, n = 32) who progressed after ICIs were included in this pooled analysis, 40 of whom had received anlotinib plus docetaxel and 31 received docetaxel. Median follow-up for all patients was 27.0 months (IQR, 17.6-31.2). A significant PFS benefit was observed with anlotinib plus docetaxel (5.4 months; 95% CI, 5.0-9.3) over docetaxel alone (2.3 months; 95% CI, 1.4-2.9), with a hazard ratio (HR) of 0.34 (95% CI, 0.18-0.63; P < 0.001). Improvement in PFS was seen across most evaluated subgroups. Anlotinib plus docetaxel induced a higher ORR (25.0% vs. 12.9%) and DCR (82.5% vs. 45.2%) over docetaxel alone. Median OS was similar between two arms (16.2 vs. 13.7 months; HR = 0.82 [0.47-1.44]; P = 0.488). Subsequent therapy with ICIs was associated with a longer OS. The incidence of grade 3 or higher treatment-related adverse events was 32.5% with anlotinib plus docetaxel and 6.5% with docetaxel. Conclusions: Anlotinib plus docetaxel demonstrated survival and response improvements compared with docetaxel alone in patients with advanced NSCLC progressing after ICIs, with a manageable safety profile. This finding suggested anlotinib plus docetaxel might be effective and safe option in this setting. Clinical trial information: NCT03726736 ; NCT03624309 .