Therapeutic outcomes of PD-1 blockade-related regimens versus docetaxel in previously immunotherapy-treated advanced non-small cell lung cancer: a retrospective, exploratory study

BACKGROUND: The optimal treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) following progression on initial immune checkpoint inhibitors (ICIs) therapy remained poorly defined. The present study aimed to identify the therapeutic outcomes of PD-1 blockade-based regimens versus docetaxel in previously immunotherapy-treated advanced NSCLC retrospectively. METHODS: Patients with advanced NSCLC who failed prior PD-1/PD-L1 blockades therapy between January 2019 and December 2025 were screened retrospectively. A total of 64 patients who received PD-1 blockade-related regimens (PD-1 blockades plus chemotherapy or PD-1 blockades plus anlotinib) were treated as observation group (OG), while 63 patients who received docetaxel single-agent were deemed as control group (CG). Therapeutic outcomes including objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and treatment related adverse events (TRAEs) were compared between the two groups. RESULTS: ORR of the 64 patients who received PD-1 blockade-based regimens in OG was 26.6% compared with 15.9% of the 63 patients who received docetaxel monotherapy in CG (P = 0.141). DCR was significantly higher in OG at 82.8% compared with 54.0% in CG (P < 0.001). The median DoR of responders in the OG and CG was 7.1 months (95%CI: 2.5-11.7) and 3.1 months (95%CI: 1.9-4.3), respectively (P = 0.056). The median PFS of 64 patients in OG and 63 patients in CG was 6.5 months and 3.3 months, respectively (P = 0.008). Similarly, the median OS was dramatically longer with PD-1 blockade-related regimens versus docetaxel group (median OS: 16.8 vs. 9.5 months, P = 0.013). After adjustment for available prognostic factors including best response to prior ICIs therapy, the treatment effect remained directionally consistent for DCR, PFS and OS, whereas ORR remained statistically non-significant. The adjusted estimates were as follows: ORR, adjusted OR = 1.85, 95%CI: 0.72-4.81, P = 0.209; DCR, adjusted OR = 4.01, 95%CI: 1.56-10.42, P = 0.004; PFS, adjusted HR = 0.59, 95%CI: 0.38-0.89, P = 0.011; and OS, adjusted HR = 0.62, 95%CI: 0.39-0.93, P = 0.020. TRAEs of any grade occurred in 82.8% of patients receiving PD-1 blockade-related regimens vs. 81.0% of patients receiving docetaxel monotherapy, and grade ≥ 3 TRAEs in OG and CG was 42.2% and 34.9%, respectively. Common TRAEs in both groups included fatigue, nausea/vomiting and hematologic toxicity. CONCLUSION: PD-1 blockade-based regimens were associated with promising disease-control and survival outcomes compared with docetaxel monotherapy with an acceptable safety profile among patients with previously ICIs-treated advanced NSCLC in clinical practice. Given the retrospective, non-randomized and exploratory design, prospective clinical trials are warranted to confirm these findings subsequently.