辅助 - 紫杉醇 + 吉西他滨治疗切除术后胰腺导管腺癌：一项随机、开放标签、III 期临床试验的结果。
Adjuvant -Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial.
机构信息
University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
出版信息
J Clin Oncol. 2023 Apr 10;41(11):2007-2019. doi: 10.1200/JCO.22.01134. Epub 2022 Dec 15.
PURPOSE
This randomized, open-label trial compared the efficacy and safety of adjuvant -paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430).
METHODS
We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to -paclitaxel (125 mg/m) + gemcitabine (1,000 mg/m) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety.
RESULTS
Two hundred eighty-seven of 432 patients and 310 of 434 patients completed -paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; = .0091). Eighty-six percent (-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events.
CONCLUSION
The primary end point (independently assessed DFS) was not met despite favorable OS seen with -paclitaxel + gemcitabine.
目的
本随机、开放标签试验比较了辅助性紫杉醇+吉西他滨与吉西他滨治疗切除的胰腺导管腺癌的疗效和安全性（ClinicalTrials.gov 标识符：NCT01964430）。
方法
我们将 866 名未经治疗的胰腺导管腺癌患者随机分配至紫杉醇（125mg/m）+吉西他滨（1000mg/m）组或吉西他滨单药组，每组接受 6 个 28 天周期中的 1 个 30-40 输注。主要终点为独立评估的无病生存期（DFS）。其他终点包括研究者评估的 DFS、总生存期（OS）和安全性。
结果
432 名患者中的 287 名和 434 名患者中的 310 名分别完成了紫杉醇+吉西他滨和吉西他滨治疗。在主要数据截止日期（2018 年 12 月 31 日；中位随访时间 38.5[四分位距[IQR]，33.8-43 个月），独立评估的中位 DFS 为 19.4 个月（紫杉醇+吉西他滨）与 18.8 个月（吉西他滨）；风险比[HR]，0.88；95%CI，0.729 至 1.063；=0.18）。研究者评估的中位 DFS 分别为 16.6（IQR，8.4-47.0）和 13.7（IQR，8.3-44.1）个月；HR，0.82；95%CI，0.694 至 0.965；=0.02）。中位 OS（427 例事件；68%成熟）分别为 40.5（IQR，20.7 至未达到）和 36.2（IQR，17.7-53.3）个月；HR，0.82；95%CI，0.680 至 0.996；=0.045）。在 16 个月的随访（截止日期，2020 年 4 月 3 日；中位随访时间，51.4 个月[IQR，47.0-57.0]）中，中位 OS（511 例事件；81%成熟）分别为 41.8 个月（紫杉醇+吉西他滨）与 37.7 个月（吉西他滨）；HR，0.82；95%CI，0.687 至 0.973；=0.0232）。在 5 年随访（截止日期，2021 年 4 月 9 日；中位随访时间，63.2 个月[IQR，60.1-68.7]）中，中位 OS（555 例事件；88%成熟）分别为 41.8 个月与 37.7 个月；HR，0.80；95%CI，0.678 至 0.947；=0.0091）。86%（紫杉醇+吉西他滨）和 68%（吉西他滨）的患者发生了≥3 级治疗相关不良事件。每个研究臂各有 2 例患者因治疗相关不良事件而死亡。
结论
尽管 OS 有利，但主要终点（独立评估的 DFS）仍未达到。
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