Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
Curr Opin Oncol. 2019 Jan;31(1):18-23. doi: 10.1097/CCO.0000000000000493.
Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15-20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic 'Holly Grail' in lung cancer treatment.
Preclinical models provide evidence of immunotherapy-radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect. The immunomodulatory and abscopal effects of radiotherapy can be further enhanced by combining with systemic immunotherapies. The phase III START trial proved that liposomal vaccine - tecemotide (L-BLP25) administered as maintenance therapy after concurrent chemoradiotherapy (CRT) in LA-NSCLC prolongs survival. In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy.
PACIFIC trial results are expected to definitely establish durvalumab as standard consolidation strategy in LA-NSCLC. Many clinical trials are ongoing in the field of immunoradiotherapy in LA-NSCLC to define the optimal conditions for this therapeutic combination.
尽管采用了基于明确的放化疗的积极治疗，不可切除的 III 期非小细胞肺癌的 5 年总生存率仍然很差（15-20%）。基于免疫检查点抑制剂（ICIs）的新型免疫疗法是肺癌治疗的治疗“圣杯”。
临床前模型提供了免疫治疗-放疗（IM-RT）协同作用的证据。电离辐射使肿瘤成为原位疫苗，启动先天免疫系统，通过克服免疫耐药肿瘤的免疫抑制微环境提高免疫治疗效果，并促进称为远隔效应的全身性、场外抗肿瘤 T 细胞介导的反应。放疗的免疫调节和远隔效应可以通过与全身免疫疗法联合进一步增强。III 期 START 试验证明，脂质体疫苗-替西莫肽（L-BLP25）在 LA-NSCLC 同步放化疗（CRT）后作为维持治疗，可以延长生存。在 III 期 PACIFIC 试验中，与抗 PD-L1 抗体度伐鲁单抗联合巩固治疗，对接受同步放化疗有反应的 LA-NSCLC 患者的生存有益。
PACIFIC 试验结果有望明确将度伐鲁单抗确立为 LA-NSCLC 的标准巩固治疗策略。许多临床试验正在进行中，以确定这种治疗联合的最佳条件。
