纳武单抗和伊匹单抗联合方案引起的不良事件。
Adverse events induced by nivolumab and ipilimumab combination regimens.
作者信息
Somekawa Kohei, Horita Nobuyuki, Kaneko Ayami, Tagami Yoichi, Fukuda Nobuhiko, Matsumoto Hiromi, Namkoong Ho, Fujiwara Yu, Minegishi Kaoru, Fukumoto Takeshi, Watanabe Keisuke, Hara Yu, Kobayashi Nobuaki, Kaneko Takeshi
机构信息
Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Pulmonology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
出版信息
Ther Adv Med Oncol. 2022 Feb 11;14:17588359211058393. doi: 10.1177/17588359211058393. eCollection 2022.
BACKGROUND
No meta-analysis has assessed the pooled frequencies of adverse events (AEs) induced by concomitant nivolumab plus ipilimumab regimen for anticancer-medications-naïve malignancies. Furthermore, no meta-analysis has compared detailed safety profiles between four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1) and four doses of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3). Objectives of this study was estimating AE frequencies, and comparison of AE frequencies between N3I1 and N1I3 regimens.
METHODS
Four major electronic databases were searched; both interventional and observational studies were included. All primary cancer types were permitted. Patients should not have been previously treated with any anti-cancer medications. The frequency of AEs was pooled using a random-model meta-analysis using the generic inverse variance method. Protocol registration: UMIN000044090.
RESULTS
Forty articles representing 48 populations with 4,677 patients were included in the study. The pooled frequencies for key indicators were as follows: any AE, 81.3% (95% confidence interval (CI) 77.5-85.1); grade 3 or higher AE, 40.6% (95% CI: 35.7-45.5); serious AE, 32.7% (95% CI: 22.4-43.1); AE leading to discontinuation, 28.3% (95% CI: 23.7-32.8); and treatment-related death, 0.7% (95% CI: 0.4-1.1). AEs with the highest incidence were fatigue (27.9%, 95% CI: 22.6-33.3), followed by diarrhea (26.0%, 95% CI: 21.5-30.5), pruritus (24.6%, 95% CI: 20.3-28.8), rash (24.0% 95% CI: 19.3-28.7), and elevated aspartate aminotransferase (21.2%, 95% CI: 14.9-27.5). Subgroup analyses demonstrated that N3I1, compared to N1I3, less frequently induced any AE (N1I3 95.7%, N3I1 84.5%, = 0.003), grade 3 or higher AE (N1I3 64.3%, N3I1 35.7%, < 0.001), and serious AE (N1I3 61.4%, N3I1 47.8%, = 0.004).
CONCLUSIONS
Approximately 40% of patients had grade 3 or higher AE. The N3I1 regimen was substantiated to trigger fewer any AEs, high grade AEs, and serious AE than the N1I3 regimen.
背景
尚无荟萃分析评估初治癌症患者接受纳武利尤单抗联合伊匹木单抗方案诱导的不良事件（AE）合并发生率。此外，尚无荟萃分析比较每3周一次给予4剂纳武利尤单抗3mg/kg联合伊匹木单抗1mg/kg（N3I1）与每3周一次给予4剂纳武利尤单抗1mg/kg联合伊匹木单抗3mg/kg（N1I3）的详细安全性。本研究的目的是估计AE发生率，并比较N3I1和N1I3方案之间的AE发生率。
方法
检索了四个主要电子数据库；纳入了干预性和观察性研究。允许所有原发性癌症类型。患者此前不应接受过任何抗癌药物治疗。使用通用逆方差法的随机模型荟萃分析汇总AE发生率。方案注册号：UMIN000044090。
结果
本研究纳入了代表48个群体4677例患者的40篇文章。关键指标的合并发生率如下：任何AE，81.3%（95%置信区间（CI）77.5-85.1）；3级或更高等级AE，40.6%（95%CI：35.7-4,5.5）；严重AE，32.7%（95%CI：22.4-43.1）；导致停药的AE，28.3%（95%CI：23.7-32.8）；以及治疗相关死亡，0.7%（95%CI：0.4-1.1）。发生率最高的AE是疲劳（27.9%，95%CI：22.6-33.3），其次是腹泻（26.0%，95%CI：21.5-30.5）、瘙痒（24.6%，95%CI：20.3-28.8）、皮疹（24.0%，95%CI：19.3-28.7）和天冬氨酸转氨酶升高（21.2%，95%CI：14.9-27.5）。亚组分析表明，与N1I3相比，N3I1诱导任何AE（N1I3 95.7%，N3I1 84.5%，P=0.003）、3级或更高等级AE（N1I3 64.3%，N3I1 35.7%，P<0.001）以及严重AE（N1I3 61.4%，N3I1 47.8%，P=0.004）的频率更低。
结论
约40%的患者发生3级或更高等级AE。证实N3I1方案比N1I3方案引发的任何AE、高级别AE和严重AE更少。
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