Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2024 Jan 17;30(2):269-273. doi: 10.1158/1078-0432.CCR-23-2124.
On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma. The approval was based on the results from the HIMALAYA study, in which patients with unresectable hepatocellular carcinoma who were naïve to previous systemic treatment were randomly assigned to receive one of three study arms: tremelimumab in combination with durvalumab (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared with sorafenib met statistical significance with a stratified HR of 0.78 [95% confidence interval (CI), 0.66-0.92; P = 0.0035]. The median OS was 16.4 months (95% CI, 14.2-19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3-16.1) with sorafenib. Adverse reactions occurring in ≥20% of patients receiving tremelimumab in combination with durvalumab were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and abdominal pain. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg, i.v., as a single dose in combination with durvalumab 1,500 mg at cycle 1/day 1, followed by durvalumab 1,500 mg, i.v., every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg, i.v., as a single dose in combination with durvalumab 20 mg/kg, i.v., followed by durvalumab 20 mg/kg, i.v., every 4 weeks.
2022 年 10 月 21 日，美国食品药品监督管理局（FDA）批准 tremelimumab（Imjudo）与 durvalumab 联合用于不可切除的肝细胞癌成人患者。该批准基于 HIMALAYA 研究的结果，该研究中，既往未接受过系统治疗的不可切除肝细胞癌患者被随机分配至以下三个研究治疗组之一： tremelimumab 联合 durvalumab（n=393）、durvalumab（n=389）或 sorafenib（n=389）。tremelimumab 联合 durvalumab 与 sorafenib 相比，总生存期（OS）的改善达到了统计学意义，分层 HR 为 0.78[95%置信区间（CI），0.66-0.92；P=0.0035]。tremelimumab 联合 durvalumab 的中位 OS 为 16.4 个月（95%CI，14.2-19.6），而 sorafenib 的中位 OS 为 13.8 个月（95%CI，12.3-16.1）。接受 tremelimumab 联合 durvalumab 治疗的患者中，发生率≥20%的不良反应有皮疹、疲劳、腹泻、瘙痒、肌肉骨骼疼痛和腹痛。体重≥30kg 患者的推荐 tremelimumab 剂量为 300mg，静脉输注，单次剂量联合 durvalumab 1500mg，第 1 周期第 1 天，随后 durvalumab 1500mg，静脉输注，每 4 周 1 次。体重＜30kg 的患者的推荐 tremelimumab 剂量为 4mg/kg，静脉输注，单次剂量联合 durvalumab 20mg/kg，静脉输注，随后 durvalumab 20mg/kg，静脉输注，每 4 周 1 次。
