Department of Hematology, Oncology and Tumorimmunology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
J Clin Oncol. 2022 Jan 1;40(1):72-82. doi: 10.1200/JCO.21.01332. Epub 2021 Sep 17.
The randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with wild-type metastatic colorectal cancer.
Following first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival, objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher's exact test; odds ratios were indicated when appropriate. The trial is registered with ClinicalTrials.gov (NCT01991873).
Overall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cutoff, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 months 5.7 months; HR, 0.72; 80% CI, 0.60 to 0.85; = .014). Overall survival (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 months 25.7 months; HR, 0.84; 95% CI, 0.60 to 1.18; = .32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (odds ratio, 1.96; 95% CI, 1.14 to 3.36; = .02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%).
In wild-type metastatic colorectal cancer, maintenance therapy with FU/FA plus Pmab induced a significantly superior PFS compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.
PANAMA 是一项随机临床试验，旨在研究帕尼单抗（Pmab）联合氟尿嘧啶和亚叶酸（FU/FA）维持治疗对野生型转移性结直肠癌患者的疗效。
在一线诱导治疗中，患者接受了 6 个周期的 FU/FA 和奥沙利铂联合 Pmab 治疗，缓解（稳定疾病或部分或完全缓解）的患者（n=248）按 1:1（开放标签）随机分配接受 FU/FA 联合 Pmab 或 FU/FA 维持治疗。主要终点是 FU/FA 联合 Pmab 维持治疗的无进展生存期（PFS，从随机分组到进展或死亡的时间）优于 FU/FA 单药维持治疗，目标是 HR 为 0.75，效能为 80%，显著性水平为 10%。次要终点包括总生存期、维持治疗的客观缓解率和毒性。生存终点采用 Kaplan-Meier 法分析，并通过对数秩检验和 Cox 回归进行比较。二分类变量采用 Fisher 确切检验进行比较；适当时采用比值比表示。该试验在 ClinicalTrials.gov 注册（NCT01991873）。
共有 248 例患者随机分配接受 FU/FA 联合 Pmab（n=125）或 FU/FA 单药（n=123）维持治疗。截至数据截止时，218 例事件（需要 218 例）中，FU/FA 联合 Pmab 维持治疗的 PFS 显著改善（8.8 个月 5.7 个月；HR，0.72；95%CI，0.60 至 0.85； =.014）。总生存期（事件率 54%）数值上有利于 FU/FA 联合 Pmab 组（28.7 个月 25.7 个月；HR，0.84；95%CI，0.60 至 1.18； =.32）。接受 FU/FA 联合 Pmab 治疗的患者客观缓解率为 40.8%，而接受 FU/FA 单药治疗的患者为 26.0%（比值比，1.96；95%CI，1.14 至 3.36； =.02）。维持治疗期间最常见的≥3 级不良事件为皮肤反应（7.2%）。
在野生型转移性结直肠癌患者中，与 FU/FA 单药维持治疗相比，FU/FA 联合 Pmab 维持治疗可显著改善 PFS。如果在 FU/FA 和奥沙利铂联合 Pmab 诱导治疗后希望进行积极的维持治疗，FU/FA 联合 Pmab 似乎是最有利的选择。
