近日，意大利圣拉斐尔科学研究所Massimo Falconi团队比较了I-III期可切除和交界性可切除胰腺导管腺癌术前接受mFOLFIRINOX与PAXG的效果。这一研究成果于2025年11月20日发表在《柳叶刀》杂志上。

围手术期化疗是可切除和交界性可切除胰腺导管腺癌（PDAC）患者治疗的标准选择。该研究旨在评估PAXG（顺铂、nab-紫杉醇、卡培他滨和吉西他滨）在该人群中是否优于mFOLFIRINOX（改性氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂）。

CASSANDRA是一个随机的、开放标签的、22因子3期试验，涉及17家意大利学术医院。符合条件的患者年龄为18-75岁，病理证实可切除或边缘性可切除PDAC。随机化由基于网络的中央系统执行，使用计算机化算法的R-代码列表。设计采用1:1随机分组，以中心和碳水化合物抗原19-9为块分层。参与者首先随机分配PAXG（每日总剂量为1250mg/m²，卡培他滨剂量为625mg/m²，每日两次，静脉注射顺铂30mg/m²， nab-紫杉醇150mg/m²，吉西他滨800mg/m²，每14天）或mFOLFIRINOX（静脉注射氟尿嘧啶2400mg/m²，亚叶酸钙400mg/m²，伊立替康150mg/m²，奥沙利铂85mg/m²，每14天），为期4个月，随后第二次随机分配至术前或术后2个月的额外化疗。主要终点是意向治疗人群的无事件生存期（EFS），安全人群包括所有接受至少一个周期指定治疗的患者。第一次随机化的结果报告在此。

2020年11月3日至2024年4月24日期间，132名符合条件的患者被分配到PAXG组，128名患者被分配到mFOLFIRINOX组。PAXG组中位年龄65岁（IQR 60-70）， 132例患者中女性68例（52%），男性64例（48%）。mFOLFIRNOX组中位年龄为63岁（IQR 57-69）， 128例患者中62例（48%）为女性，66例（52%）为男性。所有260例患者均接受了至少一次指定化疗。与mFOLFIRINOX相比，PAXG延长了中位EFS（16.0个月vs 10.2个月[8.6 - 13.5]；风险比为0.63 [0.47 - 0.84];p= 0.0018）。PAXG组132例患者中有87例（66%）和mFOLFIRINOX组128例患者中有78例（61%）至少观察到一次3级或更严重的不良事件，包括一次致命事件。

研究结果表明，与mFOLFIRINOX相比，PAXG可显著改善可切除或边缘性可切除PDAC的EFS。术前PAXG可被视为可切除或边缘性可切除PDAC的标准选择。因此，术前PAXG应被视为未来试验的标准比较组。

附：英文原文

Title: Preoperative mFOLFIRINOX versus PAXG for stage I–III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2×2 factorial phase 3 trial

Author: Michele Reni, Marina Macchini, Giulia Orsi, Letizia Procaccio, Giuseppe Malleo, Catia Carconi, Ilario Giovanni Rapposelli, Katia Bencardino, Mario Scartozzi, Gianpaolo Balzano, Domenico Tamburrino, Barbara Merelli, Elisa Sperti, Giulio Belfiori, Nicole Liscia, Silvia Bozzarelli, Mariacristina Di Marco, Emiliano Tamburini, Michele Milella, Sara Lonardi, Giorgio Ercolani, Michele Mazzola, Diego Palumbo, Valter Torri, Massimo Falconi

Issue&Volume: 2025-11-20

Abstract:

Background

Perioperative chemotherapy is a standard option for treatment of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). This study aimed to assess the superiority of PAXG (cisplatin, nab-paclitaxel, capecitabine, and gemcitabine) over mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) in this population.

Methods

CASSANDRA is a randomised, open-label, 2×2 factorial phase 3 trial, involving 17 Italian academic hospitals. Eligible patients were aged 18–75 years with pathologically confirmed resectable or borderline resectable PDAC. Randomisation was performed by a central web-based system using R-code lists with a computerised algorithm. The design adopted a 1:1 randomisation, with a block stratification by centre and carbohydrate antigen 19-9. Participants were first randomly assigned PAXG (total daily capecitabine dose of 1250 mg/m2 in a 625 mg/m2 twice a day dosage and intravenous cisplatin 30 mg/m2, nab-paclitaxel 150 mg/m2, and gemcitabine 800 mg/m2 every 14 days) or mFOLFIRINOX (intravenous fluorouracil 2400 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2, and oxaliplatin 85 mg/m2 every 14 days) for 4 months, followed by a second randomisation to 2 months of additional chemotherapy either before or after surgery. The primary endpoint was event-free survival (EFS) in the intention-to-treat population and the safety population included all patients who received at least one cycle of the assigned therapy. The results of the first randomisation are reported here. The trial, registered on ClinicalTrials.gov (NCT04793932) and EudraCT (2020-003080-26 and 2024-519031-42-00), completed accrual and reached the necessary events for first randomisation primary analysis but follow-up of overall survival is ongoing.

Findings

Between Nov 3, 2020, and April 24, 2024, 132 eligible patients were assigned to PAXG and 128 to mFOLFIRINOX. In the PAXG group, the median age was 65 years (IQR 60–70), 68 (52%) of 132 patients were female, and 64 (48%) were male. In the mFOLFIRNOX group, the median age was 63 years (IQR 57–69), 62 (48%) of 128 patients were female, and 66 (52%) were male. All 260 patients received at least one assigned chemotherapy administration. PAXG prolonged the median EFS compared with mFOLFIRINOX (16·0 months [95% CI 12·4–19·8] vs 10·2 months [8·6–13·5]; hazard ratio 0·63 [0·47–0·84]; p=0·0018). At least one grade 3 or worse adverse event was observed in 87 (66%) of 132 patients in the PAXG group and in 78 (61%) of 128 patients in the mFOLFIRINOX group, including one fatal event.

Interpretation

PAXG significantly improved EFS compared with mFOLFIRINOX in resectable or borderline resectable PDAC. Preopertive PAXG could be considered a standard option for resectable or borderline resectable PDAC. Accordingly, preoperative PAXG should be considered as the standard comparator group for future trials in this setting.

DOI: 10.1016/S0140-6736(25)01685-X

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01685-X/abstract