Juravinski Cancer Center, McMaster University, Hamilton, ON, Canada.
Tom Baker Cancer Center, Cummings School of Medicine, University of Calgary, Calgary, AB, Canada.
Lung Cancer. 2020 May;143:1-11. doi: 10.1016/j.lungcan.2020.02.016. Epub 2020 Feb 28.
This multicenter phase Ib study aimed to establish a recommended phase II dose for durvalumab (Du) ± tremelimumab (Tr) in combination with standard platinum-doublet chemotherapy. Eligible patients were enrolled into one of six dose levels (DL) of Du ± Tr which included concomitant treatment with standard platinum-doublet regimens; (pemetrexed, gemcitabine, etoposide, (each with cisplatin or carboplatin) or nab-paclitaxel (with carboplatin)). Dose escalation was according to a Rolling Six type design. Both weight-based and fixed dosing of Du and Tr were explored. Du was continued until progression. Tr dosing was finite (up to 6 doses) with increasing dose and/or frequency by DL. 136 patients were enrolled. The majority of drug-related adverse events (AEs) were ≤ grade 2 and attributable to chemotherapy. AEs considered related to immunotherapy were mainly ≤ grade 2; the most frequent (occurring ≥10 %) were colitis/diarrhea, skin, and thyroid dysfunction. Seven patients had DLTs including pneumonitis, myocarditis, diarrhea, encephalitis, motor neuropathy, and enterocolitis. There were 2 treatment-related deaths. Tr and Du exposures did not appear affected by chemotherapy. Among the 73 non-small cell lung cancer (NSCLC) patients treated, the objective response rate was 51 % (95 %CI = 38.7-62.6 %) with a median progression-free and overall survival of 6.5 months (95 % CI = 5.5-9.4 months) and 19.8 months (95 % CI = 14.8 months - not yet reached) respectively. Anti-tumour activity was observed across PD-L1 subtypes. Du 1500 mg q3w and Tr 75 mg q3wx5 can be safely combined with platinum-doublet chemotherapy. Efficacy among NSCLC patients appears comparable to results from other immunotherapy and chemotherapy combination trials. NCT02537418.
这项多中心 Ib 期研究旨在确定度伐利尤单抗（Du）联合标准铂类双联化疗的推荐 II 期剂量。符合条件的患者被纳入六个剂量水平（DL）之一的 Du ± Tr 治疗组，包括标准铂类双联化疗方案（培美曲塞、吉西他滨、依托泊苷、顺铂或卡铂）或nab-紫杉醇（卡铂））；同时接受治疗。剂量递增采用滚动六型设计。Du 和 Tr 的剂量均根据体重和固定剂量进行探索。Du 持续使用直至疾病进展。Tr 剂量有限（最多 6 剂），随着剂量和/或 DL 的增加而增加。共纳入 136 例患者。大多数药物相关不良事件（AE）为≤2 级，与化疗相关。与免疫治疗相关的 AE 主要为≤2 级；最常见的（发生频率≥10%）为结肠炎/腹泻、皮肤和甲状腺功能障碍。7 例患者发生 DLT，包括肺炎、心肌炎、腹泻、脑炎、运动神经病和结肠炎。有 2 例治疗相关死亡。Tr 和 Du 的暴露似乎不受化疗影响。在 73 例非小细胞肺癌（NSCLC）患者中，客观缓解率为 51%（95%CI=38.7-62.6%），中位无进展生存期和总生存期分别为 6.5 个月（95%CI=5.5-9.4 个月）和 19.8 个月（95%CI=14.8 个月-尚未达到）。在 PD-L1 各亚组中均观察到抗肿瘤活性。Du 1500mg q3w 和 Tr 75mg q3wx5 联合铂类双联化疗安全可行。在 NSCLC 患者中的疗效与其他免疫治疗和化疗联合试验的结果相当。NCT02537418。
