Mimura Kosaku, Ogata Takashi, Yoshimoto Yuya, Yoshida Daisaku, Nakajima Shotaro, Sato Hisashi, Machida Nozomu, Yamada Takanobu, Watanabe Yohei, Tamaki Tomoaki, Fujikawa Hirohito, Inokuchi Yasuhiro, Hayase Suguru, Hanayama Hiroyuki, Saze Zenichiro, Katoh Hiroyuki, Takahashi Fumiaki, Oshima Takashi, Suzuki Yoshiyuki, Kono Koji
Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan.
Commun Med (Lond). 2023 Aug 15;3(1):111. doi: 10.1038/s43856-023-00343-4.
Although immune checkpoint inhibitors (ICI) targeting for PD-1 axis is a promising approach for advanced gastric cancer (GC) patients, the response rate is still limited. Induction of synergistic effect of irradiation with ICI targeting for the PD-1 axis can be an attractive strategy. The aim of this study was to assess the effect of the combination of irradiation with anti-PD-1 therapy for advanced GC.
We conducted a single-arm, phase I/II trial in GC patients treated with a combination of nivolumab and oligo-fractionated irradiation (22.5 Gy/5 fractions/5 days) (NCT03453164). Eligible patients (n = 40) had unresectable advanced or recurrent GC which progressed after primary and secondary chemotherapy with more than one lesion. The primary endpoint is the disease control rate (DCR) of non-irradiated target lesions and the secondary endpoints are the median survival time (MST), safety, and DCR of irradiated lesions.
We observe that the DCR for the non-irradiated target as the abscopal effect is 22.5% (90% confidence interval (CI), 12.3-36.0), and the DCR for the irradiated lesion is 40.0% (90% CI, 26.9-54.2). The median survival time is 230 days (95% CI, 157-330), and grade 3 and higher adverse events (AEs) are observed in 16 patients (39 %) with no obvious additional AEs when adding irradiation.
The present study suggests that the combination of nivolumab with oligo-fractionated irradiation has the potential to induce a promising anti-tumor effect for advanced GC.
尽管针对PD-1轴的免疫检查点抑制剂（ICI）是晚期胃癌（GC）患者的一种有前景的治疗方法，但其缓解率仍然有限。诱导针对PD-1轴的ICI与放疗的协同效应可能是一种有吸引力的策略。本研究的目的是评估放疗联合抗PD-1治疗对晚期GC的疗效。
我们对接受纳武单抗和低分割放疗（22.5 Gy/5次/5天）联合治疗的GC患者进行了一项单臂I/II期试验（NCT03453164）。符合条件的患者（n = 40）患有不可切除的晚期或复发性GC，在一线和二线化疗后进展，且有多个病灶。主要终点是非照射靶病灶的疾病控制率（DCR），次要终点是中位生存时间（MST）、安全性以及照射病灶的DCR。
我们观察到作为远隔效应的非照射靶病灶的DCR为22.5%（90%置信区间（CI），12.3 - 36.0），照射病灶的DCR为40.0%（90% CI，26.9 - 54.2）。中位生存时间为230天（95% CI，157 - 330），16例患者（39%）出现3级及以上不良事件（AE），放疗后未观察到明显的额外AE。
本研究表明，纳武单抗与低分割放疗联合应用有可能对晚期GC产生有前景的抗肿瘤作用。
