Miyamoto Shingo, Nomura Ryutaro, Sato Kengo, Awano Nobuyasu, Kuse Naoyuki, Inomata Minoru, Izumo Takehiro, Terada Yuriko, Furuhata Yoshiaki, Bae Yuan, Kunitoh Hideo
Department of Medical Oncology, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.
CyberKnife Center, Japanese Red Cross Medical Center, Shibuya, Tokyo, Japan.
Jpn J Clin Oncol. 2019 Feb 1;49(2):160-164. doi: 10.1093/jjco/hyy171.
Radiation therapy might modify the cancer immune environment to enhance the antitumor effect of immune checkpoint inhibitors. We performed a feasibility study of nivolumab following stereotactic radiation therapy for chemotherapy pretreated advanced non-small-cell lung cancer.
Pretreated advanced/recurrent non-small-cell lung cancer patients received stereotactic radiation therapy to one of the disease sites. Nivolumab at a dose of 3 mg/kg was given within 2 weeks after the completion of stereotactic radiation therapy and continued every 2 weeks thereafter until disease progression or unacceptable toxicities. The primary endpoint was the occurrence rate of Grade 3 pneumonitis (within 12 weeks) or other non-hematological toxicity (within 8 weeks).
From September 2016 to September 2017, six patients were enrolled. Five received stereotactic radiation therapy to their primary lesions. All patients received nivolumab on the following day after stereotactic radiation therapy completion. Grade 3 pneumonitis occurred in one patient, but no other serious adverse events were reported for the other patients. One complete response and two partial responses were achieved. Four patients had measurable lesions outside the irradiated area, of whom three patients responded to the treatment. The initial progression sites were mainly outside the irradiated field, including one brain metastasis.
Nivolumab therapy immediately following stereotactic radiation therapy was well tolerated. This sequential combination warrants further study.
放射治疗可能会改变癌症免疫环境，以增强免疫检查点抑制剂的抗肿瘤效果。我们对接受过化疗的晚期非小细胞肺癌患者进行立体定向放射治疗后使用纳武利尤单抗进行了一项可行性研究。
接受过治疗的晚期/复发性非小细胞肺癌患者对其中一个病灶部位接受立体定向放射治疗。在立体定向放射治疗完成后的2周内给予剂量为3mg/kg的纳武利尤单抗，此后每2周持续给药，直至疾病进展或出现不可接受的毒性反应。主要终点是3级肺炎（12周内）或其他非血液学毒性（8周内）的发生率。
2016年9月至2017年9月，纳入6例患者。5例对其原发灶接受了立体定向放射治疗。所有患者在立体定向放射治疗完成后的次日接受纳武利尤单抗治疗。1例患者发生3级肺炎，但其他患者未报告其他严重不良事件。获得1例完全缓解和2例部分缓解。4例患者在照射区域外有可测量病灶，其中3例患者对治疗有反应。初始进展部位主要在照射野之外，包括1例脑转移。
立体定向放射治疗后立即进行纳武利尤单抗治疗耐受性良好。这种序贯联合治疗值得进一步研究。
