Maintenance with 5-FU/LV-aflibercept after induction with FOLFIRI-aflibercept versus FOLFIRI-aflibercept until progression as second-line treatment in older adults with metastatic colorectal cancer: the AFEMA phase II randomized trial

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-11-27 DOI:10.1016/j.esmoop.2024.103986

P. García-Alfonso , E. Elez , J. Soto-Alsar , D. Páez , A. Fernández-Montes , B. Graña , A. Salud , A. Yubero , M.A. Gómez-España , I. Macías , G. Quintero , C. López-López , T. Fernández-Rodríguez , C. Grávalos , E. González-Flores , M. Guix , B. García Paredes , J.J. Reina , J.R. Rodríguez Mowbray , J. Sastre , E. Aranda

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引用次数: 0

Abstract

Background

The combination chemotherapy i.v. 5-fluorouracil (5-FU), irinotecan, and aflibercept (FOLFIRI-A) is a standard second-line treatment of metastatic colorectal cancer (mCRC). The aim was to assess maintenance treatment in second-line setting in older patients (aged ≥70 years) with mCRC.

Patients and methods

We evaluated FOLFIRI-A given for six cycles followed by maintenance with 5-FU/leucovorin (LV)-A (arm A) or FOLFIRI-A (arm B) until progression in older adults with mCRC in the AFEMA randomized, open-label, non-inferiority phase II trial (EudraCT2016-004076-21/NCT03279289). Patients aged ≥70 years who previously failed oxaliplatin-fluoropyrimidine were randomly allocated (1 : 1) to either arm A (experimental) or arm B (control). After enrolling 35 patients, the FOLFIRI dose was reduced to level 1 in both arms due to toxicity. The primary endpoint was median progression-free survival (PFS); and secondary endpoints were median overall survival, objective response rate, and safety. Non-inferiority required the upper confidence interval (CI) limit to not exceed a hazard ratio (HR) of 1.5 (one-sided α = 0.075, 80% power).

Results

A total of 170 patients were randomly allocated to arm A or arm B (n = 85 each). The median follow-up was 12.2 versus 10.9 months in arm A versus arm B. Most patients died (83.5% versus 88.2% in arm A versus arm B), mainly from disease progression. PFS non-inferiority was met (HR = 0.78, 95% CI 0.566-1.076, P = 0.131) with a median PFS of 6.1 versus 5.5 months in arm A versus arm B. Median overall survival was similar in arms A and B (12.2 and 11.5 months, respectively) (HR = 0.89, 95% CI 0.640-1.227, P = 0.467). During the maintenance phase, severe asthenia (4.5% versus 21.6%, P = 0.038), serious adverse events (SAEs) (17.8% versus 37.8%, P = 0.049), and treatment-related SAEs (6.7% versus 10.8%, P = 0.695) were reduced in arm A versus arm B.

Conclusion

In older adults, induction with six cycles of FOLFIRI-A plus maintenance with 5-FU/LV-A was non-inferior to FOLFIRI-A until progression. Severe asthenia, SAEs, and treatment-related SAEs were reduced with 5-FU/LV-A maintenance.

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老年转移性结直肠癌患者在接受 FOLFIRI-aflibercept 与 FOLFIRI-aflibercept 诱导治疗后继续使用 5-FU/LV-aflibercept 与 FOLFIRI-aflibercept 直到病情进展作为二线治疗的对比：AFEMA II 期随机试验

背景静脉注射5-氟尿嘧啶（5-FU）、伊立替康和阿弗利百普（FOLFIRI-A）联合化疗是转移性结直肠癌（mCRC）的标准二线治疗方法。患者和方法我们在AFEMA随机、开放标签、非劣效II期试验（EudraCT2016-004076-21/NCT03279289）中评估了老年mCRC患者在给予FOLFIRI-A治疗6个周期后使用5-FU/亮菌甲素（LV）-A（A组）或FOLFIRI-A（B组）维持治疗直至病情进展的情况。年龄≥70岁、既往奥沙利铂-氟嘧啶治疗失败的患者被随机分配（1:1）至A组（实验组）或B组（对照组）。35名患者入组后，由于毒性问题，两组的FOLFIRI剂量均降至1级。主要终点是中位无进展生存期（PFS）；次要终点是中位总生存期、客观反应率和安全性。非劣效性要求置信区间（CI）上限不超过1.5的危险比（HR）（单侧α=0.075，80%功率）。大多数患者死亡（A 组 83.5% 对 B 组 88.2%），主要死于疾病进展。A 组与 B 组的中位总生存期相似（分别为 12.2 个月和 11.5 个月）（HR = 0.89，95% CI 0.640-1.227，P = 0.467）。在维持治疗阶段，A 组与 B 组相比，严重气喘（4.5% 对 21.6%，P = 0.038）、严重不良事件（SAE）（17.8% 对 37.8%，P = 0.049）和治疗相关 SAE（6.7% 对 10.8%，P = 0.695）均有所减少。5-FU/LV-A维持治疗可减少严重气喘、SAE和治疗相关SAE。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.