Mouri Atsuto, Imai Hisao, Endo Satoshi, Nakagawa Junichi, Tsukamoto Kasumi, Kurata Yuhei, Yamaguchi Ou, Masaki Kenji, Hashimoto Kosuke, Shiono Ayako, Miura Yu, Kobayashi Kunihiko, Kaira Kyoichi, Kagamu Hiroshi
Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Hidaka, Japan.
Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan.
Cancer Med. 2025 Apr;14(8):e70741. doi: 10.1002/cam4.70741.
The combination of nivolumab and ipilimumab, which act on different immune checkpoint molecules, is a promising first-line treatment strategy for advanced nonsmall cell lung cancer (NSCLC). However, real-world clinical data on this regimen, particularly regarding the relationship between adverse events (AEs) and efficacy, are inadequate.
This real-world retrospective study was conducted on patients with advanced or recurrent NSCLC treated using a combination of nivolumab and ipilimumab as a first-line treatment. We extracted the data of consecutive eligible patients from four institutions in Japan between December 2020 and November 2022.
The study population comprised 184 patients who received nivolumab plus ipilimumab (median follow up period: 13.0 months [0.3-35.0]). In total, 81.0% (n = 149) of the patients were men, and the median age was 72.0 years (range: 46-80). The median progression-free survival (PFS) and overall survival (OS) were 6.6 months (95% confidence interval [CI]: 4.7-8.2) and 17.4 months (95% CI: 11.9-20.4), respectively. Skin disorders, liver dysfunction, thyroid dysfunction, and pneumonitis were the most common adverse events (AEs), with AEs occurring in 154 patients (83.7%). The median PFS in the AE group was longer than that in the non-AE group (8.2 vs. 2.6 months, p < 0.0001). The median OS in the AE group was also better than that in the non-AE group (19.3 vs. 6.1 months, p < 0.0001). Multivariate logistic regression analysis identified smoking history and high PD-L1 expression as factors related to the incidence of grade 3 and 4 AEs, respectively. The incidence of multiple AEs revealed a significant association with a longer PFS and OS. Skin disorders, adrenal insufficiency, and eosinophilia were the AEs with the greatest impact on survival.
Patients who experienced AEs had significantly longer PFS. Among AEs, the occurrence of skin disorders, adrenal insufficiency, and eosinophilia were likely to prolong PFS and OS.
纳武利尤单抗和伊匹木单抗作用于不同的免疫检查点分子，二者联合使用是晚期非小细胞肺癌（NSCLC）一种有前景的一线治疗策略。然而，关于该治疗方案的真实世界临床数据，尤其是不良事件（AE）与疗效之间的关系，并不充分。
本真实世界回顾性研究针对使用纳武利尤单抗和伊匹木单抗联合作为一线治疗的晚期或复发性NSCLC患者开展。我们从2020年12月至2022年11月期间日本四个机构连续纳入符合条件的患者数据。
研究人群包括184例接受纳武利尤单抗加伊匹木单抗治疗的患者（中位随访期：13.0个月[0.3 - 35.0]）。总体上，81.0%（n = 149）的患者为男性，中位年龄为72.0岁（范围：46 - 80岁）。中位无进展生存期（PFS）和总生存期（OS）分别为6.6个月（95%置信区间[CI]：4.7 - 8.2）和17.4个月（95% CI：11.9 - 20.4）。皮肤疾病、肝功能障碍、甲状腺功能障碍和肺炎是最常见的不良事件（AE），154例患者（83.7%）发生了AE。AE组的中位PFS长于非AE组（8.2个月对2.6个月，p < 0.0001）。AE组的中位OS也优于非AE组（19.3个月对6.1个月，p < 0.0001）。多因素逻辑回归分析确定吸烟史和高PD - L1表达分别为与3级和4级AE发生率相关的因素。多种AE的发生率与更长的PFS和OS显著相关。皮肤疾病、肾上腺功能不全和嗜酸性粒细胞增多症是对生存影响最大的AE。
发生AE的患者PFS显著更长。在AE中，皮肤疾病、肾上腺功能不全和嗜酸性粒细胞增多症的发生可能会延长PFS和OS。
