論文No4099
Evaluating the safety of antibody-drug conjugates in lung cancer: A systematic review and meta-analysis
Qi He,Lin Jiang,Yan Xu,Mengzhao Wang
LUN CANCER, Volume 201, 108425, March 2025.
要約
この研究では、肺がん患者における抗体薬物複合体（ADC）治療の有害事象（AE）を包括的に評価しました。
3,127人の患者を対象とした28件の研究のメタアナリシスにより、
全グレードのAEはほぼすべての患者に発生し、重篤なAEも高頻度に見られました。
消化器系、血液系、呼吸器系が主な影響を受ける器官系であり、特に呼吸器系の有害事象は死亡や薬剤中止の主な原因でした。
また、小細胞肺がん、併用療法、特定のADC成分（切断可能なリンカー、特定の標的タンパク質やペイロード）は、有害事象のリスクを高めることが示されました。
Take Home Message
肺がんに対するADC治療は、高い有効性が期待される一方で、有害事象のリスクも高い。
特に、呼吸器系の有害事象には注意が必要であり、綿密なモニタリングが不可欠である。
患者の病理学的タイプ、治療レジメン、およびADCの構成要素を考慮して、リスクを最小限に抑えるための個別化された管理戦略が重要である。
消化器系、感染症にも注意し、早期発見早期対応が重要である。
Background
Antibody-drug conjugates (ADC) have emerged as a promising treatment for lung cancer. However, their safety profile requires further analysis. This study assessed adverse events (AE) in patients with lung cancer treated with ADCs, with particular focus on differences in pathological types, therapeutic options, and drug components.
Methods
Prospective trials from various databases up to June 11, 2024, that analyzed treatment-emergent AEs (TEAEs), treatment-related AEs (TRAEs), mortality, and drug discontinuation were identified. Incidence rates were pooled using a random effects model, and their corresponding 95% confidence intervals (CIs) were calculated.
Results
The analysis included 28 studies with 3,127 participants. The pooled incidence of all-grade TEAEs and TRAEs was 98.9 % and 91.4 %, respectively, whereas that of grade ≥ 3 TEAEs and TRAEs was 65.9 % and 41.7 %, respectively. The gastrointestinal system was frequently involved, albeit predominantly in low grades. Hematological system involvement was prevalent in grade ≥ 3 AEs, with respiratory system disorders being more prevalent in severe AEs. Respiratory system disorders were the primary cause of death and drug discontinuation. Subgroup analyses revealed higher incidences of AEs in SCLC than in NSCLC, in combination therapies than in monotherapies, and in ADCs with cleavable linkers. ADCs targeting delta-like protein 3 or carrying pyrrolobenzodiazepine dimer as payloads exhibit higher incidences of grade ≥ 3 TEAEs than those targeting HER2.
Conclusion
Effective managing ADC toxicities is crucial in lung cancer treatment, with AE incidence and profiles varying by cancer pathology, treatment regimen, and ADC components. Close monitoring of symptoms associated with gastrointestinal, infection, and respiratory systems is essential.