PRODIGE 24/CCTG PA.6 是一项多中心随机 3 期临床试验。从 2012 年 4 月~ 2016 年 10 月，77 个中心 493 例接受过 R0 或者 R1 切除术的胰腺导管腺癌患者入组，A 组接受标准吉西他滨单药四周方案 6 个周期，B 组接受 mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m² D1, and 5-FU 2.4 g/m² over 46 h) 12 周期。
研究结果: 研究主要终点 DFS 分别为 A 组 12.8 个月 vs B 组 21.6 m, HR = 0.59 (95% CI, 0.47-0.74). 次要终点 OS 分别为 34.8 vs 54.4 m 个月, HR = 0.66 (95% CI, 0.49-0.89). 次要终点无转移生存时间 MFS 分别为 17.7 vs 30.4 个月, HR = 0.59(95% CI, 0.46-0.76)。
笔者点评: 这将是今年 ASCO 胰腺癌最令人的难忘的研究，胰腺癌的辅助治疗竟然真的采用 3 药联合方案，而且两组之间的差异之大，已经远远超过既往 ESPAC 和 JASPC 的一系列研究。
辅助治疗领域里，mFOLFIRNOX 这匹黑马，与 GEM+xeloda 和 GEM+S1，究竟如何选择，恐怕在今后一段时间内都会成为讨论的话题。该研究的口头报告芝加哥当地时间 6 月 4 日下午，患者人群和不良反应预计将会成为现场讨论的焦点。
另附摘要
Background: FOLFIRINOX is more effective than gem as first-line treatment in metastatic pancreatic cancer for patients (pts) with good performance status. This trial assessed the benefit of mFOLFIRINOX in the adjuvant setting. Methods: PRODIGE 24/CCTG PA.6 is a phase III multicenter, randomized clinical trial.
Pts aged 18-79 years with histologically proven pancreatic ductal adenocarcinomas, 21-84 days after R0 or R1 resection, WHO PS ≤ 1, adequate hematologic and renal function, and no cardiac ischemia, were eligible. Randomization was stratified by center, pN, R margin status, and post-operative CA 19-9 level (≤ 90 U/mL vs 91-180).
Arm A pts received 28-day cycles of gem on days 1, 8, and 15 for 6 cycles. Arm B pts received mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m² D1, and 5-FU 2.4 g/m² over 46 h) every 14 days for 12 cycles. Primary endpoint was disease-free survival (DFS).
Secondary endpoints were overall survival (OS), metastasis-free survival (MFS), and adverse events (AE). 490 pts were required to observe 342 events to show a gain in 3-year DFS from 17% to 27% (HR = 0.74) with a two-sided α = 0.05 and 80% power. Hazard ratios (HR) and 95% CI were estimated by a stratified Cox proportional hazard model.
We observed 91.5% of the events required. The IDMC approved early ITT analysis before March 15, 2018. Surgical procedures, pathology and postoperative CT scans reports were centrally reviewed. Results: From Apr 2012 to Oct 2016, 493 pts were enrolled in 77 centers: Arm A/B: 246/247.
With a median follow up of 30.5 months [m] (95% CI, 29.5-33.7), median DFS was 12.8 (95% CI, 11.7-15.2) in Arm A vs 21.6 m (95% CI, 17.5-26.7) in Arm B, HR = 0.59 (95% CI, 0.47-0.74). The median OS (Arm A/B) was 34.8 (95% CI, 28.6-43.8) vs 54.4 m (95% CI, 41.5- --), HR = 0.66 (95% CI, 0.49-0.89).
The median MFS (Arm A/B) was 17.7 (95% CI, 14.2-21.7) vs 30.4 m (95% CI, 21.6- --), HR = 0.59 (95% CI, 0.46-0.76). Grade 3-4 AE (Arm A/B) were reported in 51.1% vs 75.5%, including 12% grade 4 in each arm, with a toxic death in Arm A. Conclusion: Adjuvant mFOLFIRINOX is safe and significantly improves DFS, MFS and OS compared to gem. Clinical trial information: NCT01526135
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