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.

IF 9.6 1区医学 Q1 MEDICINE, GENERAL & INTERNAL

EClinicalMedicine Pub Date : 2024-12-16 eCollection Date: 2025-01-01 DOI:10.1016/j.eclinm.2024.103004

Arndt Stahler, Meinolf Karthaus, Stefan Fruehauf, Ullrich Graeven, Lothar Müller, Ludwig Fischer von Weikersthal, Karel Caca, Eray Goekkurt, Alexej Ballhausen, Greta Sommerhäuser, Annabel H S Alig, Swantje Held, Armin Jarosch, David Horst, Anke Reinacher-Schick, Stefan Kasper, Volker Heinemann, Sebastian Stintzing, Tanja Trarbach, Dominik P Modest

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引用次数: 0

Abstract

Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated RAS 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), P = 0.015), shorter PFS re-ind. (4.1 versus 7.4 months, HR = 1.93 (95% CI 1.33-2.82), P < 0.001), comparable TFS (17.1 versus 15.7 months, HR = 0.98 (95% CI 0.68-1.42), P = 0.92) and numerically longer OS (29.9 versus 24.7 months, HR = 0.85 (95% CI 0.64-1.12), P = 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.

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Panitumumab联合5-氟尿嘧啶和亚叶酸或单独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（巴拿马，AIO KRK 0212）：一项随机、开放标签、2期试验的最终疗效分析。

背景：巴拿马试验旨在比较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RAS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FU/FA、奥沙利铂和帕尼单抗六个周期有反应的成年mCRC患者被随机（1:1，开放标签）分配到FU/FA +帕尼单抗或FU/FA单独维持。主要终点是无进展维持生存(PFS；从随机分配到进展/死亡的时间)支持FU/FA +帕尼单抗。次要终点包括再诱导PFS （PFS re-ind.）、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月期间招募的248例完整分析集患者中，治疗组的中位观察时间为64.0（12.5-86.3）个月和59.7（3.7-97.3）个月，记录了230例PFS事件（92.7%）和196例OS事件（79.0%）。在FU/FA中加入帕尼珠单抗显著延长了PFS(8.8个月vs 5.8个月，HR = 0.73 (95% CI 0.56-0.94), P = 0.015)，缩短了PFS的复发期。（4.1对7.4个月，HR = 1.93 (95% CI 1.33-2.82), P = 0.92）和更长的OS（29.9对24.7个月，HR = 0.85 (95% CI 0.64-1.12), P = 0.24）。最常见的不良事件(AE)≥3级为皮疹（FU/FA +帕尼单抗：n = 15,12.0%, FU/FA: n = 17,6.9%）。141例（37.3%）患者发生了至少一次严重AE 1例治疗相关死亡（中性粒细胞减少性败血症，FU/FA）。解释：帕尼珠单抗加FU/FA可能被认为是一种标准的护理维持方案，因为在维持治疗决策时，帕尼珠单抗不能保证潜在的再诱导治疗。资金:安进公司。

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来源期刊

EClinicalMedicine Medicine-Medicine (all)

CiteScore

18.90

自引率

1.30%

发文量

506

审稿时长

22 days

期刊介绍： eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.