Higashiyama Tomoki, Kuribayashi Kozo, Doi Hiroshi, Kubota Aki, Otsuki Taiichiro, Nakajima Yasuhiro, Mikami Koji, Takahashi Ryo, Nakamura Akifumi, Fujimoto Daichi, Kitajima Kazuhiro, Minami Toshiyuki, Kijima Takashi, Kuribayashi Kozo
Department of Respiratory Medicine and Hematology, Hyogo Medical University, Nishinomiya, Japan.
Department of Radiation Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
Oncology. 2025;103(9):805-814. doi: 10.1159/000543414. Epub 2025 Jan 24.
In August 2018, the Japanese PMDA approved nivolumab, an immune checkpoint inhibitor, for previously treated, unresectable, advanced, or recurrent pleural mesothelioma (PM) based on the MERIT trial, a phase II study of 34 cases. However, concerns regarding limited evidence persist.
We retrospectively analyzed 83 patients with previously treated, unresectable, advanced, or recurrent malignant PM treated with nivolumab from August 2018 to May 2022. Efficacy was evaluated using overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) per modified RECIST criteria. Safety was assessed by treatment-related adverse events (TRAEs) according to CTCAE v5.0. PD-L1 expression was analyzed with the anti-PD-1 antibody (22C3).
The median age was 73 years. Histological subtypes included epithelioid (60), sarcomatoid (15), biphasic (6), and unknown (2). Lines of treatment were 2nd (62), 3rd (13), and 4th or later (8). Partial response was seen in 16 patients, stable disease in 30, progressive disease in 29, and not evaluable in 8, with an ORR of 19.3% and a disease control rate of 55.4%. Median PFS and OS were 5.1 and 12.4 months, respectively. TRAEs occurred in 45 patients (54.2%), with grade ≥3 in 6 (7.2%) and one treatment-related death. PFS correlated with male gender, TRAEs, and good performance status (PS: 0-1), while OS correlated with PS.
Nivolumab demonstrated efficacy and safety in clinical practice, supporting its use in patients with good PS, even in later lines.
2018年8月，基于一项针对34例患者的II期研究MERIT试验，日本药品和医疗器械管理局（PMDA）批准将免疫检查点抑制剂纳武单抗用于先前接受过治疗、无法切除、晚期或复发性胸膜间皮瘤（PM）。然而，关于证据有限的担忧依然存在。
我们回顾性分析了2018年8月至2022年5月期间接受纳武单抗治疗的83例先前接受过治疗、无法切除、晚期或复发性恶性PM患者。根据改良的RECIST标准，使用总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）评估疗效。根据CTCAE v5.0，通过治疗相关不良事件（TRAEs）评估安全性。使用抗PD-1抗体（22C3）分析PD-L1表达。
中位年龄为73岁。组织学亚型包括上皮样（60例）、肉瘤样（15例）、双向性（6例）和未知（2例）。治疗线数为二线（62例）、三线（13例）和四线及以后（8例）。16例患者出现部分缓解，30例病情稳定，29例病情进展，8例不可评估，ORR为19.3%，疾病控制率为55.4%。中位PFS和OS分别为5.1个月和12.4个月。45例患者（54.2%）发生TRAEs，6例（7.2%）为≥3级，1例与治疗相关死亡。PFS与男性、TRAEs和良好的体能状态（PS：0-1）相关，而OS与PS相关。
纳武单抗在临床实践中显示出疗效和安全性，支持其用于体能状态良好的患者，即使是在后续治疗线中。
