帕尼单抗联合氟尿嘧啶和亚叶酸治疗与单用氟尿嘧啶和亚叶酸维持治疗对 RAS WT 转移性结直肠癌（mCRC）患者疗效和安全性的影响：PanaMa 研究（AIO-KRK-0212）的亚组分析。
Impact of sex on the efficacy and safety of panitumumab plus fluorouracil and folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS WT metastatic colorectal cancer (mCRC). Subgroup analysis of the PanaMa-study (AIO-KRK-0212).
机构信息
Department of Medicine III, University Hospital, LMU Munich, Munich; German Cancer Consortium (DKTK), Partner Site Munich, Munich. Electronic address: https://twitter.com/heinrich_kat.
Department of Hematology and Oncology, Munich Hospital Neuperlach, Munich.
出版信息
ESMO Open. 2023 Aug;8(4):101568. doi: 10.1016/j.esmoop.2023.101568. Epub 2023 Jul 11.
BACKGROUND
Clinical trials in metastatic colorectal cancer (mCRC) are usually conducted irrespective of sex. Sex-associated differences relating to safety and efficacy in the treatment of mCRC, however, are gaining interest.
METHODS
PanaMa investigated the efficacy of panitumumab (Pmab) plus fluorouracil and folinic acid (FU/FA) versus FU/FA alone after induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab in patients with RAS wild-type mCRC. In this post hoc analysis, the study population was stratified for sex. Evaluated efficacy endpoints during maintenance treatment were progression-free survival (PFS, primary endpoint of the trial), overall survival (OS) and objective response rate during maintenance therapy. Safety endpoints were rates of any grade and grade 3/4 adverse events during maintenance therapy.
RESULTS
In total, 165 male and 83 female patients were randomized and treated. Male and female patients showed numerically better objective response rates with Pmab, without reaching statistical significance. Male patients derived a significant benefit from the addition of Pmab to maintenance treatment with regard to PFS [hazard ratio (HR) 0.63; 95% confidence interval (CI) 0.45-0.88; P = 0.006] that was not observed in female patients (HR 0.85; 95% CI 0.53-1.35; P = 0.491). The better PFS for male patients treated with Pmab did not translate into improved OS (HR 0.85; 95% CI 0.55-1.30; P = 0.452). Female patients showed numerically improved OS when treated with Pmab. There was no difference in the total of grade ≥3 adverse events during maintenance regarding sex (P = 0.791). Female patients, however, had a higher rate of any grade nausea, diarrhea and stomatitis.
CONCLUSIONS
In the PanaMa trial, the addition of Pmab to maintenance treatment of RAS wild-type mCRC with FU/FA improved the outcome in terms of the primary endpoint (PFS) particularly in male patients. Female patients did not show the same benefit while experiencing higher rates of adverse events. Our results support the development of sex-specific protocols.
背景
转移性结直肠癌（mCRC）的临床试验通常不考虑性别。然而，与 mCRC 治疗安全性和疗效相关的性别差异正引起关注。
方法
PanaMa 研究了在接受六个周期氟尿嘧啶/亚叶酸（FU/FA）和奥沙利铂联合 panitumumab（Pmab）诱导治疗后，Pmab 联合 FU/FA 对比单独 FU/FA 用于 RAS 野生型 mCRC 患者维持治疗的疗效。在这项事后分析中，根据性别对研究人群进行分层。维持治疗期间评估的疗效终点为无进展生存期（PFS，试验的主要终点）、总生存期（OS）和维持治疗期间的客观缓解率。安全性终点为维持治疗期间任何级别和 3/4 级不良事件的发生率。
结果
共有 165 名男性和 83 名女性患者被随机分配并接受治疗。接受 Pmab 治疗的男性和女性患者客观缓解率略有提高，但无统计学意义。与女性患者相比，男性患者从 Pmab 联合维持治疗中显著获益，PFS 得到改善[风险比（HR）0.63；95%置信区间（CI）0.45-0.88；P=0.006]，而女性患者未观察到这种获益（HR 0.85；95% CI 0.53-1.35；P=0.491）。接受 Pmab 治疗的男性患者的 PFS 改善并未转化为 OS 改善（HR 0.85；95% CI 0.55-1.30；P=0.452）。接受 Pmab 治疗的女性患者 OS 略有改善。两组患者维持治疗期间≥3 级不良事件总发生率无差异（P=0.791）。然而，女性患者的任何级别恶心、腹泻和口腔炎发生率更高。
结论
在 PanaMa 试验中，在 RAS 野生型 mCRC 患者中，FU/FA 联合 Pmab 维持治疗可改善主要终点（PFS）的疗效，尤其在男性患者中。然而，女性患者并未获得相同的获益，同时发生不良事件的风险更高。我们的结果支持制定特定性别方案。
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