Palmer Daniel H, Jackson Richard, Springfeld Christoph, Ghaneh Paula, Rawcliffe Charlotte, Halloran Christopher M, Faluyi Olusola, Cunningham David, Wadsley Jonathan, Darby Suzanne, Meyer Tim, Gillmore Roopinder, Lind Pehr, Glimelius Bengt, Falk Stephen, Ma Yuk Ting, Middleton Gary William, Cummins Sebastian, Ross Paul J, Wasan Harpreet, McDonald Alec, Crosby Tom, Hammel Pascal, Borg David, Sothi Sharmila, Valle Juan W, Mehrabi Arianeb, Bailey Peter, Tjaden Christine, Michalski Christoph, Hackert Thilo, Büchler Markus W, Neoptolemos John P
University of Liverpool, Liverpool, United Kingdom.
Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.
J Clin Oncol. 2025 Apr;43(10):1240-1253. doi: 10.1200/JCO.24.01118. Epub 2024 Dec 5.
The ESPAC4 trial showed that adjuvant chemotherapy with gemcitabine plus capecitabine (GemCap) produced longer overall survival (OS) than gemcitabine monotherapy. Subsequently, the PRODIGE24-CCTG PA.6 trial showed even longer survival for modified fluorouracil, folinic acid, irinotecan, and oxaliplatin (mFOLFIRINOX) than gemcitabine but had more restrictive eligibility criteria. Our aim was to analyze the ESPAC4 survival on long-term follow-up.
The OS of 732 ESPAC4 patients comparing 367 randomly assigned to gemcitabine and 365 to GemCap was previously reported after a median follow-up time of 43.2 months (95% CI, 39.7 to 45.5) and 458 deaths. Analysis was now carried out after a median follow-up of 104 months (101-108) and 566 deaths.
The median OS was 29.5 months (27.5-32.1) for all patients, 28.4 months (25.2-32.0) in the gemcitabine group and 31.6 months (26.5-38.0) in the GemCap group (hazard ratio [HR], 0.83 [0.71 to 0.98]; = .031). R0 patients given gemcitabine had a median survival of 32.2 months (27.9-41.6) compared with 49.9 months (39.0-82.3) for those given GemCap (HR, 0.63 [0.47 to 0.84]; = .002). Lymph node-negative patients had significantly higher 5 year OS rates on GemCap (59% [49%-71%]) than gemcitabine (53% [42%-66%]; HR, 0.63 [0.41 to 0.98]; = .04) but not those with positive lymph nodes ( = .225). The OS advantage for GemCap was retained in the PRODIGE24 subgroup of 193 (26.4%) ESPAC4 patients not eligible for PRODIGE24 with a median survival of 20.7 (16.2-27.3) months in patients allocated to gemcitabine compared with 25.9 (22.3-30.2) months for ineligible patients allocated to GemCap (HR, 0.71 [95% CI, 0.52 to 0.98]; χ = 4.31; = .038).
GemCap is a standard option for patients not eligible for mFOLFIRINOX. Exploratory evidence suggests that GemCap may be particularly efficacious in R0 patients and also in lymph node-negative patients.
ESPAC4试验表明，吉西他滨联合卡培他滨（GemCap）辅助化疗的总生存期（OS）长于吉西他滨单药治疗。随后，PRODIGE24-CCTG PA.6试验表明，改良氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂（mFOLFIRINOX）方案的生存期比吉西他滨更长，但入选标准更为严格。我们的目的是分析ESPAC4试验长期随访后的生存情况。
之前报道了ESPAC4研究中732例患者的OS，其中367例随机分配接受吉西他滨治疗，365例接受GemCap治疗，中位随访时间为43.2个月（95%CI，39.7至45.5），458例死亡。现在在中位随访104个月（101-108）、566例死亡后进行分析。
所有患者的中位OS为29.5个月（27.5-32.1），吉西他滨组为28.4个月（25.2-32.0），GemCap组为31.6个月（26.5-38.0）（风险比[HR]，0.83[0.71至0.98]；P = 0.031）。接受吉西他滨治疗的R0患者中位生存期为32.2个月（27.9-41.6），而接受GemCap治疗的患者为49.9个月（39.0-82.3）（HR，0.63[0.47至0.84]；P = 0.002）。淋巴结阴性患者接受GemCap治疗的5年OS率（59%[49%-71%]）显著高于吉西他滨治疗（53%[42%-66%]；HR，0.63[0.41至0.98]；P = 0.04），但淋巴结阳性患者无差异（P = 0.225）。在193例（26.4%）不符合PRODIGE24入选标准的ESPAC4患者的PRODIGE24亚组中，GemCap的OS优势依然存在，分配接受吉西他滨治疗的患者中位生存期为20.7（16.2-27.3）个月，而分配接受GemCap治疗的不符合入选标准患者为25.9（22.3-30.2）个月（HR，0.71[95%CI，0.52至0.98]；χ = 4.31；P = 0.038）。
GemCap是不符合mFOLFIRINOX治疗标准患者的标准选择。探索性证据表明，GemCap可能对R0患者以及淋巴结阴性患者特别有效。
