Psyrri A, Fayette J, Harrington K, Gillison M, Ahn M-J, Takahashi S, Weiss J, Machiels J-P, Baxi S, Vasilyev A, Karpenko A, Dvorkin M, Hsieh C-Y, Thungappa S C, Segura P P, Vynnychenko I, Haddad R, Kasper S, Mauz P-S, Baker V, He P, Evans B, Wildsmith S, Olsson R F, Yovine A, Kurland J F, Morsli N, Seiwert T Y
Department of Internal Medicine, Section of Medical Oncology, Attikon University Hospital, National Kapodistrian University of Athens, Athens, Greece.
Centre de Lutte Contre le Cancer Léon Bérard, Lyon-I University, Lyon, France.
Ann Oncol. 2023 Mar;34(3):262-274. doi: 10.1016/j.annonc.2022.12.008. Epub 2022 Dec 16.
Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC.
Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed.
Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively.
In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.
复发性或转移性头颈部鳞状细胞癌（R/M HNSCC）患者预后较差。III期KESTREL研究评估了度伐利尤单抗[程序性死亡配体1（PD-L1）抗体]联合或不联合曲美木单抗[细胞毒性T淋巴细胞相关抗原4（CTLA-4）抗体]对比EXTREME方案治疗R/M HNSCC患者的疗效。
未接受过R/M疾病一线全身治疗的HNSCC患者按2:1:1随机分组，分别接受度伐利尤单抗1500mg每4周一次（Q4W）联合曲美木单抗75mg Q4W（最多4剂）、度伐利尤单抗单药1500mg Q4W或EXTREME方案（铂类、5-氟尿嘧啶和西妥昔单抗），直至疾病进展。评估度伐利尤单抗无论联合或不联合曲美木单抗对比EXTREME方案在PD-L1高表达肿瘤患者及所有随机分组患者中的疗效。同时评估安全性。
在PD-L1高表达患者中，度伐利尤单抗及度伐利尤单抗联合曲美木单抗的总生存期（OS）不优于EXTREME方案[中位数分别为10.9、11.2和10.9个月；风险比（HR）=0.96；95%置信区间（CI）0.69-1.32；P=0.787以及HR=1.05；95%CI 0.80-1.39]。度伐利尤单抗及度伐利尤单抗联合曲美木单抗的缓解持续时间长于EXTREME方案（12个月时仍处于缓解的患者比例分别为49.3%、48.1%和9.8%），与缓解患者的长期OS相关；然而，EXTREME方案的中位无进展生存期更长（2.8、2.8和5.4个月）。探索性分析表明，EXTREME方案组24.3%的患者后续使用免疫治疗促成了两组相似的OS结果。度伐利尤单抗、度伐利尤单抗联合曲美木单抗及EXTREME方案的3/4级治疗相关不良事件（TRAEs）分别为8.9%、19.1%和53.1%。
在PD-L1高表达患者中，度伐利尤单抗与EXTREME方案的OS相当。在R/M HNSCC中，度伐利尤单抗单药及联合曲美木单抗与EXTREME方案相比，显示出持久的缓解且TRAEs减少。
