Sangro B, Chan S L, Kelley R K, Lau G, Kudo M, Sukeepaisarnjaroen W, Yarchoan M, De Toni E N, Furuse J, Kang Y K, Galle P R, Rimassa L, Heurgué A, Tam V C, Van Dao T, Thungappa S C, Breder V, Ostapenko Y, Reig M, Makowsky M, Paskow M J, Gupta C, Kurland J F, Negro A, Abou-Alfa G K
Liver Unit and HPB Oncology Area, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain.
State Key Laboratory of Translational Oncology, Department of Clinical Oncology, Sir Yue-Kong Pao Center for Cancer, The Chinese University of Hong Kong, Hong Kong SAR, China.
Ann Oncol. 2024 May;35(5):448-457. doi: 10.1016/j.annonc.2024.02.005. Epub 2024 Feb 19.
In the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a 4-year updated OS analysis of HIMALAYA.
Participants with uHCC and no previous systemic treatment were randomized to STRIDE (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The updated data cut-off was 23 January 2023. OS and serious adverse events (AEs) were assessed. Additionally, baseline characteristics and subsequent therapies were analyzed in long-term survivors (≥36 months beyond randomization).
For STRIDE, durvalumab, and sorafenib, median [95% confidence interval (CI)] follow-up was 49.12 months (46.95-50.17 months), 48.46 months (46.82-49.81 months), and 47.31 months (45.08-49.15 months), respectively. OS hazard ratio (95% CI) for STRIDE versus sorafenib was 0.78 (0.67-0.92). The 36-month OS rate for STRIDE was 30.7% versus 19.8% for sorafenib. The 48-month OS rate remained higher for STRIDE at 25.2%, versus 15.1% for sorafenib. The long-term OS benefit of STRIDE was observed across clinically relevant subgroups and was further improved in participants who achieved disease control. Long-term survivors with STRIDE (n = 103) included participants across clinically relevant subgroups, and 57.3% (59/103) had no reported subsequent anticancer therapy. No new serious treatment-related AEs occurred with STRIDE from the primary analysis (17.5%; 68/388). Durvalumab maintained OS noninferiority to sorafenib and no late-onset safety signals were identified.
These data represent the longest follow-up to date in phase III studies in uHCC. The unprecedented 3- and 4-year OS rates reinforce the sustained long-term OS benefit of STRIDE versus sorafenib. STRIDE maintained a tolerable yet differentiated safety profile from other current uHCC therapies. Results continue to support the long-term benefits of STRIDE in a diverse population, reflective of uHCC globally.
在不可切除肝细胞癌（uHCC）的III期喜马拉雅研究（NCT03298451）中，STRIDE（单药曲美木单抗定期联合度伐利尤单抗）与索拉非尼相比显著改善了总生存期（OS）；度伐利尤单抗单药治疗在OS方面不劣于索拉非尼。本文报告的结果来自喜马拉雅研究的4年OS更新分析。
未接受过全身治疗的uHCC患者被随机分为STRIDE组（n = 393）、度伐利尤单抗组（n = 389）或索拉非尼组（n = 389）。更新数据截止日期为2023年1月23日。评估了OS和严重不良事件（AE）。此外，对长期生存者（随机分组后≥36个月）的基线特征和后续治疗进行了分析。
对于STRIDE组、度伐利尤单抗组和索拉非尼组，中位[95%置信区间（CI）]随访时间分别为49.12个月（46.95 - 50.17个月）、48.46个月（46.82 - 49.81个月）和47.31个月（45.08 - 49.15个月）。STRIDE组与索拉非尼组的OS风险比（95%CI）为0.78（0.67 - 0.92）。STRIDE组的36个月OS率为30.7%，而索拉非尼组为19.8%。STRIDE组的48个月OS率仍较高，为25.2%，而索拉非尼组为15.1%。在临床相关亚组中均观察到STRIDE的长期OS获益，且在实现疾病控制的参与者中进一步改善。接受STRIDE治疗的长期生存者（n = 103）包括临床相关亚组的参与者，57.3%（59/103）未报告后续抗癌治疗。初步分析中STRIDE未出现新的严重治疗相关AE（17.5%；68/388）。度伐利尤单抗维持了OS不劣于索拉非尼的效果，且未发现迟发性安全信号。
这些数据代表了uHCC III期研究迄今为止最长的随访时间。前所未有的3年和4年OS率强化了STRIDE对比索拉非尼持续的长期OS获益。STRIDE与其他当前uHCC治疗相比，维持了可耐受但有差异的安全性。结果继续支持STRIDE在不同人群中的长期获益，反映了全球uHCC的情况。
