Anlotinib Plus Docetaxel is Promising in Advanced NSCLC Progressing on First-Line Immunotherapy: A Pooled Analysis of Two Randomized Trials.

INTRODUCTION

Therapeutic options for patients with advanced non-small cell lung cancer (NSCLC) after progression on immune checkpoint inhibitors (ICIs) remain a significant challenge. This analysis compared outcomes of anlotinib plus docetaxel versus docetaxel alone in this population using the pooled data from two prospective randomized trials (ALTER-L016; ALTER-L018).

METHODS

Adult patients with EGFR/ALK/ROS1 wild-type advanced NSCLC progressing on first-line ICIs were eligible. Patients were randomly assigned to anlotinib plus docetaxel or docetaxel alone. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety.

RESULTS

Seventy-one patients were included in this pooled analysis (L016, n = 39; L018, n = 32), of whom, 40 received anlotinib plus docetaxel and 31 received docetaxel. The median follow-up of all patients was 27.0 months. The median PFS was longer with anlotinib plus docetaxel than with docetaxel alone (5.4 months [95% CI 5.0-9.3] vs. 2.3 months [95% CI 1.4-2.9]; hazard ratio [HR], 0.34; 95% CI 0.18-0.63; P < 0.001). Both ORR (25.0% vs. 12.9%) and DCR (82.5% vs. 45.2%) were higher in the anlotinib plus docetaxel group than in the docetaxel group. Median OS was 16.2 months (95% CI 8.3-21.3) with anlotinib plus docetaxel versus 13.7 months (95% CI 4.6-22.3) with docetaxel (HR = 0.82; 95% CI 0.47-1.44; P = 0.488). Subsequent ICI therapy was associated with a longer OS. Grade 3 treatment-related adverse events occurred in 32.5% of patients receiving anlotinib plus docetaxel and 6.5% of patients receiving docetaxel.

CONCLUSION

Anlotinib plus docetaxel improved PFS but not OS versus docetaxel in patients with advanced NSCLC progressing on ICIs. Larger standardized phase 3 trials are needed to verify these findings.

TRIAL REGISTRATION: ALTER-L016 (ClinicalTrials.gov identifier, NCT03726736). ALTER-L018 (ClinicalTrials.gov identifier, NCT03624309).