Department of Otolaryngology, UPMC Hillman Cancer Center, Pittsburgh, USA.
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, USA.
Ann Oncol. 2020 Jul;31(7):942-950. doi: 10.1016/j.annonc.2020.04.001. Epub 2020 Apr 12.
Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients.
Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks [q2w]), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w × 4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response.
Patients were randomly assigned to receive durvalumab (n = 240), durvalumab plus tremelimumab (n = 247), or SoC (n = 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72-1.08; P = 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85-1.26; P = 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9-43.1), 30.4% (24.7-36.3), and 30.5% (24.7-36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade ≥3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively.
There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab.
ClinicalTrials.gov: NCT02369874.
靶向程序性死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）轴在复发性/转移性头颈部鳞状细胞癌（R/M HNSCC）中显示出临床获益。联合使用针对 PD-L1 和细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）的免疫疗法已在多种肿瘤类型中显示出相加活性的证据。这项 III 期研究评估了度伐利尤单抗（一种抗 PD-L1 单克隆抗体）或度伐利尤单抗联合替西木单抗（一种抗 CTLA-4 单克隆抗体）与 R/M HNSCC 患者标准治疗（SoC）相比的疗效。
患者被随机分配接受 1：1：1 的度伐利尤单抗（每 2 周 10 mg/kg[q2w]）、度伐利尤单抗联合替西木单抗（度伐利尤单抗 20 mg/kg q4w 联合替西木单抗 1 mg/kg q4w×4，然后度伐利尤单抗 10 mg/kg q2w）或 SoC（西妥昔单抗、紫杉烷类药物、甲氨蝶呤或氟嘧啶）。主要终点是度伐利尤单抗与 SoC 的总生存期（OS），以及度伐利尤单抗联合替西木单抗与 SoC 的 OS。次要终点包括无进展生存期（PFS）、客观缓解率和缓解持续时间。
患者被随机分配接受度伐利尤单抗（n=240）、度伐利尤单抗联合替西木单抗（n=247）或 SoC（n=249）。与 SoC 相比，度伐利尤单抗与 OS 无统计学显著改善[风险比（HR）：0.88；95%置信区间（CI）：0.72-1.08；P=0.20]或度伐利尤单抗联合替西木单抗与 OS（HR：1.04；95%CI：0.85-1.26；P=0.76）。12 个月的生存率（95%CI）分别为 37.0%（30.9-43.1）、30.4%（24.7-36.3）和 30.5%（24.7-36.4），分别为度伐利尤单抗、度伐利尤单抗联合替西木单抗和 SoC。与治疗相关的不良事件（trAEs）与之前的报告一致。最常见的 trAEs（任何等级）为度伐利尤单抗和度伐利尤单抗联合替西木单抗的甲状腺功能减退症（11.4%和 12.2%）和 SoC 的贫血症（17.5%）。度伐利尤单抗、度伐利尤单抗联合替西木单抗和 SoC 的≥3 级 trAE 发生率分别为 10.1%、16.3%和 24.2%。
与 SoC 相比，度伐利尤单抗或度伐利尤单抗联合替西木单抗在 OS 方面无统计学显著差异。然而，12 至 24 个月时更高的生存率和缓解率表明度伐利尤单抗具有临床活性。
ClinicalTrials.gov：NCT02369874。
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