帕尼单抗联合5-氟尿嘧啶和亚叶酸或单独使用5-氟尿嘧啶和亚叶酸作为RAS野生型转移性结直肠癌的维持治疗（PanaMa，AIO KRK 0212）：一项随机、开放标签的2期试验的最终疗效分析
Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trial.
作者信息
Stahler Arndt, Karthaus Meinolf, Fruehauf Stefan, Graeven Ullrich, Müller Lothar, Fischer von Weikersthal Ludwig, Caca Karel, Goekkurt Eray, Ballhausen Alexej, Sommerhäuser Greta, Alig Annabel H S, Held Swantje, Jarosch Armin, Horst David, Reinacher-Schick Anke, Kasper Stefan, Heinemann Volker, Stintzing Sebastian, Trarbach Tanja, Modest Dominik P
机构信息
Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Hematology, Oncology and Cancer Immunology, Berlin, Germany.
Department of Hematology and Oncology, Munich Hospital Neuperlach, Munich, Germany.
出版信息
EClinicalMedicine. 2024 Dec 16;79:103004. doi: 10.1016/j.eclinm.2024.103004. eCollection 2025 Jan.
BACKGROUND
The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated wild-type metastatic colorectal cancer (mCRC) patients.
METHODS
In this final phase 2 trial analysis, adult mCRC patients responding to six cycles of FU/FA, oxaliplatin and panitumumab were randomized (1:1, open-label) to maintenance of either FU/FA + panitumumab or FU/FA alone. The primary endpoint was superiority of progression-free survival of maintenance (PFS; time from random assignment to progression/death) in favour of FU/FA + panitumumab. Secondary endpoints included PFS of re-induction (PFS re-ind.), time to failure of strategy (TFS) and overall survival (OS). The trial is registered with ClinicalTrials.gov (NCT01991873).
FINDINGS
In 248 patients of the Full Analysis Set recruited between May 2014 and February 2021, with a median observation of 64.0 (range 12.5-86.3) months and 59.7 (range 3.7-97.3) months in the treatment arms, 230 events for PFS (92.7%) and 196 events for OS (79.0%) were recorded. Adding panitumumab to FU/FA resulted in significantly longer PFS (8.8 versus 5.8 months, HR = 0.73 (95% CI 0.56-0.94), = 0.015), shorter PFS re-ind. (4.1 versus 7.4 months, HR = 1.93 (95% CI 1.33-2.82), < 0.001), comparable TFS (17.1 versus 15.7 months, HR = 0.98 (95% CI 0.68-1.42), = 0.92) and numerically longer OS (29.9 versus 24.7 months, HR = 0.85 (95% CI 0.64-1.12), = 0.24). The most frequent adverse event (AE) grade ≥3 was rash (FU/FA + panitumumab: n = 15, 12.0%, FU/FA: n = 17, 6.9%). 141 patients (37.3%) experienced at least one serious AE One treatment-related death occurred (neutropenic sepsis, FU/FA).
INTERPRETATION
Panitumumab plus FU/FA might be considered a standard of care maintenance regimen since a potential re-induction therapy with panitumumab cannot be guaranteed at the time of maintenance treatment decision.
FUNDING
Amgen.
背景
泛美（PanaMa）试验旨在比较5-氟尿嘧啶和亚叶酸（FU/FA）±帕尼单抗维持治疗在未经治疗的野生型转移性结直肠癌（mCRC）患者中的疗效。
方法
在这项最终的2期试验分析中，对接受六个周期FU/FA、奥沙利铂和帕尼单抗治疗有反应的成年mCRC患者进行随机分组（1:1，开放标签），分别接受FU/FA + 帕尼单抗或单独FU/FA维持治疗。主要终点是维持治疗的无进展生存期（PFS；从随机分组到疾病进展/死亡的时间）优势，即FU/FA + 帕尼单抗组更优。次要终点包括再诱导的PFS（PFS re-ind.）、治疗策略失败时间（TFS）和总生存期（OS）。该试验已在ClinicalTrials.gov注册（NCT01991873）。
研究结果
在2014年5月至2021年2月招募的248例全分析集患者中，治疗组的中位观察时间分别为64.0（范围12.5 - 86.3）个月和59.7（范围3.7 - 97.3）个月，记录到230例PFS事件（92.7%）和196例OS事件（79.0%）。在FU/FA基础上加用帕尼单抗可显著延长PFS（8.8个月对5.8个月，HR = 0.73（95% CI 0.56 - 0.94），P = 0.015），缩短PFS re-ind.（4.1个月对7.4个月，HR = 1.93（95% CI 1.33 - 2.82），P < 0.001），TFS相当（17.1个月对15.7个月，HR = 0.98（95% CI 0.68 - 1.42），P = 0.92），OS在数值上更长（29.9个月对24.7个月，HR = 0.85（95% CI 0.64 - 1.12），P = 0.24）。最常见的≥3级不良事件（AE）是皮疹（FU/FA + 帕尼单抗组：n = 15，12.0%；FU/FA组：n = 17，6.9%）。141例患者（37.3%）经历了至少一次严重AE。发生了一例与治疗相关的死亡（中性粒细胞减少性败血症，FU/FA组）。
解读
由于在做出维持治疗决策时不能保证使用帕尼单抗进行潜在的再诱导治疗，帕尼单抗加FU/FA可被视为一种标准的维持治疗方案。
资助
安进公司。
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