Phase III randomized controlled trial of adjuvant chemoimmunotherapy in patients with resected primary lung cancer

Abstract

Background: Adoptive cellar immunotherapy is not widely approved as a treatment option for cancer treatment. The preliminary results from our phase III, randomized controlled trial (RCT) of adjuvant chemoimmunotherapy for lung cancer indicated significant advantages in patients receiving immunotherapy. Here we report the final results and long-term analysis of this RCT. Methods: A hundred and three postsurgical non-small-cell lung cancer patients were randomly designated to receive either chemoimmunotherapy (group A, immunotherapy arm, n=51) or chemotherapy (group B, control arm, n=52). The immunotherapy consisted of adoptive transfer of autologous activated killer T cells and dendritic cells obtained from regional lymph nodes of the patients. Results: The 2- and 5-year overall survival (OS) rates were 96-0% and 69.4% in group A and 64-7% and 45.1% in group B, respectively. The hazard ratio (HR) was 0.451 (0.235-0.807) by multivariate analysis. The 2- and 5-year recurrence-free survival rates were 70.0% and 57-9% in group A and 43.1% and 31.4% in group B, respectively. P values of Log-rank test between groups were 0.0059. Subgroup analysis for the OS between treatment groups indicated males (HR, 0-474), adenocarcinoma patients (HR, 0-479), stage III cancer patients (HR, 0-399), and those who did not receive preoperative chemotherapy (HR, 0-483) had lower HRs than those in the other groups. Immunological analysis of cell surface markers in regional lymph nodes of subjects receiving immunotherapy indicated that the CD8+/CD4+ T-cell ratio was elevated in survivors. Conclusions: Non-small-cell lung cancer patients benefited from adoptive cellular immunotherapy as an adjuvant to surgery. Immunological analysis of cell surface markers indicated cytotoxic T cells were essential for a favorable chemoimmunotherapy outcome.