Fu Zhiwen, Gao Chen, Xie Jiyi, Zhang Cong, Li Shijun, Gu Ming, Shi Chen
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, 1277 Jiefang Avenue, Jianghan District, Wuhan, Hubei Province, 430000, China.
BMC Cancer. 2023 Oct 10;23(1):960. doi: 10.1186/s12885-023-11250-1.
Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been associated with several fatal adverse events, such as pneumonia, interstitial lung disease, and infection. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted ADCs.
We performed a systematic search in Embase, PubMed, Web of Science, and Scopus databases from inception to February 1, 2022, and the last search was updated to July 1, 2023. The eligible studies for inclusion in our analysis were limited to RCTs of HER2-targeted ADCs that were approved by the US Food and Drug Administration and examined on cancer patients with available data on fatal adverse events. The protocol for this study was registered in PROSPERO (No. CRD42022331627).
Fifteen studies (13 RCTs) involving 7,277 patients were finally included for meta-analysis. Of these patients, 4,246 received HER2-targeted ADCs and 3,481 received the control treatment. The data were combined using Bayesian hierarchical modeling, which allowed for the estimation of the mean incidence of fatal adverse events to be 0.78% (95% CrI: 0.28-1.37%, τ = 0.006) for the patients treated with HER2-targeted ADCs. The relative risk was 0.80 (95% CrI, 0.5-1.26, τ = 0.17) compared to control patients. Among 43 reported deaths caused by HER2-targeted ADCs, the most common fatal adverse event was respiratory toxicity, including pneumonia, pneumonitis, and interstitial lung disease. On subgroup analysis, no difference in the risk of fatal adverse events was found between different HER2-targeted ADCs or cancer types.
Our findings suggest that the risk of fatal adverse events with HER2-targeted ADCs may be lower compared to standard control therapies in cancer patients, and there is no significant difference in risk observed between different HER2-targeted ADCs or cancer types. However, the most common fatal adverse event was respiratory toxicity, suggesting that cancer patients who use the above drugs should strengthen respiratory system monitoring and take preventive measures in some severe cases.
靶向人表皮生长因子受体2（HER2）的抗体药物偶联物（ADC）引领着靶向癌症治疗的新时代。这些药物也与一些致命的不良事件相关，如肺炎、间质性肺病和感染。我们进行了一项随机对照试验（RCT）的荟萃分析，以估计接受HER2靶向ADC治疗的癌症患者中致命不良事件的发生率和风险。
我们在Embase、PubMed、Web of Science和Scopus数据库中进行了系统检索，检索时间从数据库建立至2022年2月1日，最后一次检索更新至2023年7月1日。纳入我们分析的合格研究仅限于美国食品药品监督管理局批准的HER2靶向ADC的RCT，且研究对象为有致命不良事件可用数据的癌症患者。本研究方案已在国际前瞻性注册系统（PROSPERO）注册（编号CRD42022331627）。
最终纳入15项研究（13项RCT），共7277例患者进行荟萃分析。其中，4246例患者接受HER2靶向ADC治疗，3481例患者接受对照治疗。采用贝叶斯分层模型合并数据，结果显示接受HER2靶向ADC治疗的患者中，致命不良事件的平均发生率估计为0.78%（95% CrI：0.28 - 1.37%，τ = 0.006）。与对照患者相比，相对风险为0.80（95% CrI，0.5 - 1.26，τ = 0.17）。在43例由HER2靶向ADC导致的死亡报告中，最常见的致命不良事件是呼吸毒性，包括肺炎、肺炎性疾病和间质性肺病。亚组分析显示，不同HER2靶向ADC或癌症类型之间，致命不良事件风险无差异。
我们的研究结果表明，与癌症患者的标准对照疗法相比，HER2靶向ADC导致致命不良事件的风险可能更低，且不同HER2靶向ADC或癌症类型之间观察到的风险无显著差异。然而，最常见的致命不良事件是呼吸毒性，这表明使用上述药物的癌症患者应加强呼吸系统监测，并在某些严重情况下采取预防措施。
