Cambridge University Hospitals NHS Foundation Trust (Addenbrooke's Hospital), Cambridge, UK.
Cancer Research UK-Cambridge Institute, University of Cambridge, Cambridge, UK.
Br J Cancer. 2020 Jun;122(12):1760-1768. doi: 10.1038/s41416-020-0846-2. Epub 2020 Apr 30.
Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial.
Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers.
In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70).
SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS.
ISRCTN71070888; ClinialTrials.gov (NCT03529175).
纳布紫杉醇联合吉西他滨（nabP+gemcitabine）为转移性胰腺导管腺癌（PDAC）患者带来了适度的生存获益。在 PDAC 小鼠模型中，序贯 NabP+吉西他滨方案可提高疗效；本研究在临床试验中对此假设进行了检验。
对未经治疗的转移性 PDAC 患者进行随机分组，接受nabP+吉西他滨联合治疗，吉西他滨与 nabP 在同一天给药（同期组）或序贯给药（序贯组，吉西他滨在 nabP 给药后 24 小时给药）。主要终点是无进展生存期（PFS）。次要终点是客观缓解率（ORR）、总生存期（OS）、安全性、生活质量（QoL）和预测生物标志物。
共 71 例患者接受序贯（SEQ）和 75 例同期（CON）治疗。SEQ 组和 CON 组的 6 个月 PFS 率分别为 46%和 32%。中位 PFS（5.6 个月比 4.0 个月，风险比 [HR]0.67，95%置信区间 [95%CI]0.47-0.95，p=0.022）和 ORR（52%比 31%，p=0.023）均有利于 SEQ 组；中位 OS 为 10.2 个月比 8.2 个月（HR 0.93，95%CI 0.65-1.33，p=0.70）。SEQ 组的中性粒细胞减少症发生率增加一倍，但不影响 QoL。肿瘤上皮胞苷脱氨酶（CDA）表达强阳性者从 SEQ 治疗中获益更大（PFS HR 0.31，95%CI 0.13-0.70）。
nabP+吉西他滨序贯给药可提高 PFS 和 ORR，毒性可耐受，但 OS 无显著改善。
ISRCTN71070888；ClinialTrials.gov（NCT03529175）。
