Randomized, Multicenter, Open-Label Trial of Autologous Cytokine-Induced Killer Cell Immunotherapy Plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer

Objective: This randomized, multicenter trial was designed to evaluate the efficacy of cytokine-induced killer (CIK) cell immunotherapy combination with chemotherapy in patients with advanced squamous non-small-cell lung cancer (NSCLC). Patients and Methods: In this phase II trial, 90 patients with untreated, stage IIIB/IV squamous NSCLC were randomized to autologous CIK cell immunotherapy plus gemcitabine and cisplatin (CIK-CT group, n = 45), or gemcitabine and cisplatin (CT group, n = 45). The primary endpoint was progression-free survival (PFS) evaluated by Kaplan–Meier analyses and treatment hazard ratios (HRs) with the Cox proportional hazards model. Results: After a median follow-up of 29.3 months, the median PFS was 8.7 months (95% CI, 7.1 to 10.3) in the CIK-CT group and 4.0 months (95% CI, 3.1 to 5.0) in the CT group (HR, 0.26; 95% CI, 0.16 to 0.43; P < .001). The median OS was 21.0 months (95% CI, 17.8 to 24.2) in the CIK-CT group and 10.3 months (95% CI, 7.9 to 12.1) in the CT group (HR, 0.22; 95% CI, 0.13 to 0.40; P < .001). The objective response rate was 62.2% (95% CI, 47.9% to 76.5%) in the CIK-CT group and 31.1% (95% CI, 17.4% to 44.8%) in the CT group ( P < .001). The adverse events of grade 3 or higher were 28.9% (13/45) and 42.2% (19/45) in the CIK-CT group and CT group, respectively. Conclusions: These data suggested that CIK cell immunotherapy could improve the efficacy of chemotherapy in patients with previously untreated, advanced squamous NSCLC. A large sample, multi-center randomized, phase III trial is being carried out in our hospital to further validate these findings. Trial Registration: This trial is registered as an international standard randomized trial with ClinicalTrials.gov Identifier: NCT01631357. Funding Statement: Supported by the National Key Technologies R&D Program of China grant Awards No. 2015BAI12B12 (to Xiubao Ren) and 2018YFC1313400 (to Jianchuan Xia), by the National Natural Science Foundation of China grants Awards No. 81572913 and 81872487 (to Liang Liu). Declaration of Interests: The authors reported no potential conflicts of interest. Ethics Approval Statement This study was approved by the State Food and Drug Administration of China (2006L01023), by the National Key Technologies R&D Program of China (2015BAI12B12), and by the Ethical Committee of Cancer Hospital of Tianjin Medical University, according to the guidelines of the Declaration of Helsinki. Informed consent was obtained from all subjects.