Respiratory Oncology Unit (Department of Pulmonology) and Leuven Lung Cancer Group, University Hospital KU Leuven, Leuven, Belgium.
Curr Opin Oncol. 2014 Mar;26(2):165-70. doi: 10.1097/CCO.0000000000000052.
Recent advances in our understanding of cancer immunology resulted in the development of promising therapeutic agents for either nonantigen-specific immunotherapy, for example, monoclonal antibodies targeting immune checkpoints on the T-cell lymphocyte, and antigen-specific immunotherapy or vaccination. Here, we review the recently reported results from randomized controlled trials (RCTs) with the latter approach.
Several trials indicated feasibility, safety, and potential for better patient outcomes. In resected early stage non-small-cell lung cancer, a phase II RCT with the MAGE-A3 vaccine showed a trend for improved disease-free interval (hazard ratio 0.75), now further evaluated in the large MAGRIT (MAGE-A3 as Adjuvant NSCLC Immunotherapy Trial) study. In stage III after chemoradiotherapy, the phase III START (Stimulating Targeted Antigenic Responses to NSCLC) trial with L-BLP25 vaccine resulted in a remarkable 10-month improvement in median survival in the concurrent chemoradiotherapy subgroup. In the advanced setting, the phase III study with the allogeneic tumor cell vaccine belagenpumatucel-L did not improve survival in the whole study, but interesting effects were seen in subgroups.
Recent non-small-cell lung cancer vaccination trials did not meet their primary endpoint, but showed clear patient benefits in subgroup analyses. Confirmatory trials and identifying patients who will benefit using predictive factors, will hopefully bring these approaches in the clinic in the near future.
近年来，癌症免疫学的研究进展催生了许多有前景的治疗方法，包括非抗原特异性免疫疗法，如针对 T 淋巴细胞免疫检查点的单克隆抗体，以及抗原特异性免疫疗法或疫苗接种。在此，我们对后者方法的随机对照试验（RCT）的最新报道结果进行综述。
几项试验表明，该方法具有可行性、安全性和提高患者预后的潜力。在可切除的早期非小细胞肺癌中，MAGE-A3 疫苗的 II 期 RCT 显示出无病间隔改善的趋势（危险比 0.75），目前正在更大规模的 MAGRIT（MAGE-A3 作为 NSCLC 辅助免疫治疗试验）研究中进一步评估。在放化疗后的 III 期，L-BLP25 疫苗的 III 期 START（刺激 NSCLC 靶向抗原反应）试验在同期放化疗亚组中中位生存期显著改善了 10 个月。在晚期，同种异体肿瘤细胞疫苗 belagenpumatucel-L 的 III 期研究并未改善整个研究的总生存期，但在亚组中观察到了有趣的效果。
最近的非小细胞肺癌疫苗接种试验未达到主要终点，但在亚组分析中显示出明确的患者获益。通过确认性试验和确定使用预测因素获益的患者，有望在不久的将来将这些方法应用于临床。
