Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA.
Bloomberg-Kimmel institute for Cancer Immunotherapy, Baltimore, MD, USA.
Oncologist. 2022 Nov 3;27(11):971-981. doi: 10.1093/oncolo/oyac140.
Anti-PD-(L)1 immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (aNSCLC). The clinical features, survival, and burden of toxicities of patients with aNSCLC alive >1 year from ICI initiation are poorly understood.
We defined ICI survivors as patients alive >1 year after ICI start and retrospectively reviewed demographics, treatment, and immune-related adverse events (irAEs). Long-term irAEs were defined as ongoing irAEs lasting >1 year; burden of toxicity measures were based on percentage of days a patient experienced toxicity. Using linear and logistic regression, we evaluated association between demographics and disease characteristics with burden of toxicity.
We identified 114 ICI survivors from 317 patients with aNSCLC. Half (52%) experienced an irAE of any grade, and 23.7% developed long-term irAEs. More ICI survivors with irAES in the first year had never smoked (P = .018) or received ICIs as frontline therapy (P = .015). The burden of toxicity in the first year significantly correlated with the burden of toxicity afterward (ρ = 0.72; P < .001). No patients with progressive disease had a high burden of toxicity, and they experienced 30.6% fewer days with toxicity than those with stable disease. Increased duration of therapy was associated with higher odds of experiencing toxicity. Half of ICI survivors with irAEs were still receiving treatment for unresolved irAEs at time of death or last follow-up.
Significant proportions of ICI survivors have unresolved long-term toxicities. These data support a growing need to understand long-term toxicity to optimize management of those treated with ICIs.
抗 PD-(L)1 免疫检查点抑制剂(ICI)可改善晚期非小细胞肺癌(aNSCLC)患者的生存。ICI 起始后生存超过 1 年的 aNSCLC 患者的临床特征、生存和毒性负担的了解甚少。
我们将 ICI 幸存者定义为 ICI 起始后生存超过 1 年的患者,并回顾性分析了人口统计学、治疗和免疫相关不良事件(irAE)。长期 irAE 定义为持续超过 1 年的正在发生的 irAE;毒性负担指标基于患者经历毒性的天数百分比。我们使用线性和逻辑回归评估了人口统计学和疾病特征与毒性负担之间的关联。
我们从 317 例 aNSCLC 患者中确定了 114 例 ICI 幸存者。一半(52%)患者发生任何级别的 irAE,23.7%患者发生长期 irAE。在第一年有 irAE 的更多 ICI 幸存者从未吸烟(P =.018)或接受 ICI 作为一线治疗(P =.015)。第一年的毒性负担与之后的毒性负担显著相关(ρ=0.72;P<0.001)。没有进展性疾病的患者毒性负担高,他们经历毒性的天数比稳定疾病患者少 30.6%。治疗持续时间的增加与经历毒性的几率增加相关。一半有 irAE 的 ICI 幸存者在死亡或最后一次随访时仍在接受未解决的 irAE 治疗。
相当比例的 ICI 幸存者仍有未解决的长期毒性。这些数据支持越来越需要了解长期毒性,以优化接受 ICI 治疗的患者的管理。