Lau George, Sangro Bruno, Cheng Ann-Lii, Kudo Masatoshi, Kelley Robin Kate, Tak Won Young, Gasbarrini Antonio, Reig Maria, Lim Ho Yeong, Tougeron David, De Toni Enrico N, Tam Vincent C, Mody Kabir, Gong Jun, Crysler Oxana V, Sukeepaisarnjaroen Wattana, Lipatov Oleg, Morimoto Manabu, Archambeaud Isabelle, Burgio Valentina, Phuong Le Thi Tuyet, Chao Yee, Peron Jean-Marie, Berres Marie-Luise, Ko Yoo-Joung, Ran Di, Makowsky Mallory, Negro Alejandra, Abou-Alfa Ghassan K
Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong Special Administrative Region, China.
Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
Hepatology. 2025 May 16. doi: 10.1097/HEP.0000000000001385.
In the global phase III HIMALAYA study in unresectable HCC, STRIDE significantly improved overall survival (OS) versus sorafenib; durvalumab was noninferior to sorafenib. Immune checkpoint inhibitor studies have shown an association between the occurrence of immune-mediated adverse events (imAEs) and improved OS. We assessed potential associations between the occurrence of imAEs and OS, and temporal patterns of imAEs, in HIMALAYA.
OS in participants who did and did not experience imAEs and the frequency and timing of imAEs were assessed for STRIDE and durvalumab in the safety analysis set of HIMALAYA. imAEs occurred in 139/388 (35.8%) and 64/388 (16.5%) participants with STRIDE and durvalumab, respectively; most were low grade. OS HRs (95% CI) in participants who experienced imAEs versus those who did not were 0.73 (0.56-0.95) for STRIDE and 1.14 (0.82-1.57) for durvalumab. The 36-month OS rate (95% CI) for STRIDE was 36.2% (28.1-46.7) and 27.7% (22.4-34.2) in participants who did and did not experience imAEs, respectively. The most common imAE category with STRIDE was endocrine events (16.5%). Most imAEs occurred ≤3 months after treatment initiation.
Participants who experienced imAEs with STRIDE had a numerical improvement in OS versus those who did not, which was not observed for durvalumab. Long-term OS with STRIDE was observed regardless of imAEs. Most imAEs were low grade, manageable, and occurred in the first 3 months after treatment initiation. Results continue to support the benefits of STRIDE in a diverse population that reflects unresectable HCC globally.
在针对不可切除肝细胞癌（HCC）的全球III期喜马拉雅研究中，与索拉非尼相比，STRIDE显著改善了总生存期（OS）；度伐利尤单抗不劣于索拉非尼。免疫检查点抑制剂研究表明，免疫介导的不良事件（imAE）的发生与OS改善之间存在关联。我们在喜马拉雅研究中评估了imAE的发生与OS之间的潜在关联以及imAE的时间模式。
在喜马拉雅研究的安全性分析集中，评估了接受和未经历imAE的参与者的OS以及STRIDE和度伐利尤单抗imAE的频率和时间。接受STRIDE和度伐利尤单抗治疗的参与者中，分别有139/388（35.8%）和64/388（16.5%）发生了imAE；大多数为低级别。经历imAE的参与者与未经历imAE的参与者相比，STRIDE的OS风险比（HR）（95%CI）为0.73（0.56 - 0.95），度伐利尤单抗为1.14（0.82 - 1.57）。接受STRIDE治疗的参与者中，经历和未经历imAE的患者36个月OS率（95%CI）分别为36.2%（28.1 - 46.7）和27.7%（22.4 - 34.2）。STRIDE最常见的imAE类别是内分泌事件（16.5%）。大多数imAE发生在治疗开始后≤3个月。
与未经历imAE的参与者相比，经历STRIDE诱导的imAE的参与者在OS方面有数值上的改善，而度伐利尤单抗未观察到这一现象。无论是否发生imAE，均观察到STRIDE的长期OS获益。大多数imAE为低级别，易于管理，且发生在治疗开始后的前3个月。结果继续支持STRIDE在反映全球不可切除HCC的多样化人群中的益处。
