Postsurgical chemo-immunotherapy offers improved survival rates for patients with NSCLC, compared to adjuvant chemotherapy alone, according to a small phase III study.
Postsurgical chemo-immunotherapy offers improved survival rates for patients with non–small-cell lung cancer (NSCLC), compared to adjuvant chemotherapy alone, according to the final analysis and long-term results from a small randomized, controlled phase III study in Japan. The findings were presented at the 2015 World Conference on Lung Cancer in Denver, Colorado (abstract 04.01).
Immunotherapy in the trial consisted of adoptive transfer of autologous activated killer T cells and dendritic cells from patients’ regional lymph nodes, explained lead study author Hideki Kimura, MD, PhD, of Saiseikai Narashino Hospital in Narashino City, Japan.
“The final results of the statistical and immunological analysis of the study confirmed the efficacy of immunotherapy in adjuvant treatment of lung cancer patients,” reported Dr. Kimura. A large-scale multi-institutional randomized controlled trial is needed and “inevitable” for the study’s findings to see clinical application, he said.
A total of 103 eligible patients with Stage IB–IV NSCLC who were younger than 76 years of age and who had undergone surgery for their lung cancer were enrolled between April 2007 and July 2012. Eligibility criteria also included Eastern Cooperative Oncology Group performance status of 0–1. Participants were randomly assigned to receive either chemo-immunotherapy (group A; n = 51 patients) or chemotherapy only (group B; n = 52).
The goal of the immunotherapy was to destroy micrometastases and chemotherapy-resistant clones. Tumor-draining regional lymph nodes (TDLN) without metastasis were obtained at surgery and cultured in lymphocyte medium containing IL-2. “Activated killer T cells and dendritic cells released from TDLN were harvested and transferred to the patients every month, beginning 1 week after adjuvant chemotherapy for four courses,” he said. Chemotherapy consisted of platinum doublet regimens.
Previously-reported preliminary results from the study had indicated a significant survival advantage associated with adding immunotherapy to adjuvant chemotherapy, Dr. Kimura noted. The new findings represent the final analysis and long-term results at a median-follow-up time of 42.8 months.
The 5-year overall survival (OS) rates were 74.6% for patients undergoing postsurgical chemo-immunotherapy, compared with 40.9% among patients receiving only adjuvant chemotherapy (hazard ratio [HR], 0.435; P = .0027), he reported. The 2-year OS rates in groups A and B were 96% and 64.7%, respectively.
Subgroup analysis between treatment groups indicated that HRs for median OS times associated with chemo-immunotherapy appear to be lower among patients who are male (HR, 0.351 [95% CI, 0.171–0.721]), who have tumors with adenocarcinoma rather than squamous histology (HR, 0.279 [95% CI, 0.116–0.669]), stage III disease (HR, 0.228 [95% CI, 0.092–0.564]), or who had not undergone neoadjuvant chemotherapy(HR, 0.360 [95% CI, 0.097-1.335]), Dr. Kimura said.
Regional lymph node cultures from patients who received immunotherapy were used to perform immunological analyses of cell surface markers. “Analysis indicated the ratios of CD8 vs CD4 (CD8/4) were elevated in survivors [compared to those] of the deceased,” Dr. Kimura reported.