AMALTHEA：希腊肿瘤协作组（HeCOG）前瞻性单臂研究，评估一线 FOLFIRI+阿柏西普治疗转移性结直肠癌患者 6 个月后的疗效和安全性，随后进行阿柏西普维持治疗。

AMALTHEA: Prospective, Single-Arm Study of the Hellenic Cooperative Oncology Group (HeCOG) Evaluating Efficacy and Safety of First-Line FOLFIRI + Aflibercept for 6 Months Followed by Aflibercept Maintenance in Patients With Metastatic Colorectal Cancer.

机构信息

Department of Medical Oncology, Medical School, University of Ioannina, Greece; Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN), Ioannina, Greece.

Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece.

出版信息

Clin Colorectal Cancer. 2018 Dec;17(4):e631-e637. doi: 10.1016/j.clcc.2018.06.003. Epub 2018 Jun 15.

DOI:10.1016/j.clcc.2018.06.003

PMID:29980490

Abstract

BACKGROUND

The efficacy and safety of the FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) regimen combined with aflibercept has not been studied in the first-line management of patients with metastatic colorectal cancer (mCRC).

PATIENTS AND METHODS

In the context of a prospective single-arm trial (NCT02129257), patients with mCRC received standard doses of a maximum of 12 cycles of FOLFIRI combined with aflibercept (4 mg/kg body weight delivered intravenously) every 2 weeks, followed by aflibercept maintenance. Endpoints were 12-month progression-free survival rate, efficacy, and toxicity.

RESULTS

Seventy-three fit patients were enrolled onto the study between 2014 and 2016. Median relative dose intensities administered were 0.80 for irinotecan and 1.0 for aflibercept. The most common grade 3/4 adverse events were neutropenia (13 patients, 18%), febrile neutropenia (3 patients, 4%), diarrhea (11 patients, 15%), hypertension (19 patients, 26%), proteinuria (8 patients, 11%), infections (8 patients, 11%), and mucositis (6 patients, 8%), with no toxic deaths. The objective response rate was 46.6%, significantly associated with the presence of right-sided primary, synchronous metastases, and a relapse-free interval of < 12 months (odds ratio = 3.00, 2.92, and 3.75 respectively, P ≤ .05). Intermediate infiltration by stromal core lymphocytes correlated with progression-free survival (hazard ratio = 0.40, [95% confidence interval (CI), 0.19-0.83], P = .014). At a median follow-up of 24.5 months, 12-month progression-free survival rate was 21.9% (median overall survival 20.9 months [95% CI, 16.6-29], median progression-free survival 8.4 months [95% CI, 7.4-9.3]).

CONCLUSION

The FOLFIRI + aflibercept regimen is active and tolerable; however, it failed to improve historical benchmarks of efficacy in chemonaive patients with mCRC. Preliminary data hint that this regimen has cytoreductive activity in disease with adverse biology.

摘要

背景

FOLFIRI（亚叶酸、5-氟尿嘧啶、伊立替康和奥沙利铂）联合 aflibercept 方案在转移性结直肠癌（mCRC）一线治疗中的疗效和安全性尚未得到研究。

患者和方法

在一项前瞻性单臂试验（NCT02129257）中，mCRC 患者接受标准剂量的最多 12 个周期的 FOLFIRI 联合 aflibercept（每 2 周静脉内给予 4mg/kg 体重），随后进行 aflibercept 维持治疗。主要终点为 12 个月无进展生存率、疗效和毒性。

结果

2014 年至 2016 年间，共纳入 73 例身体状况良好的患者。给予的伊立替康和 aflibercept 的中位相对剂量强度分别为 0.80 和 1.0。最常见的 3/4 级不良事件为中性粒细胞减少症（13 例，18%）、发热性中性粒细胞减少症（3 例，4%）、腹泻（11 例，15%）、高血压（19 例，26%）、蛋白尿（8 例，11%）、感染（8 例，11%）和黏膜炎（6 例，8%），无毒性死亡。客观缓解率为 46.6%，与右侧原发性、同步转移以及无疾病缓解间隔<12 个月显著相关（比值比分别为 3.00、2.92 和 3.75，P≤0.05）。间质核心淋巴细胞的中度浸润与无进展生存率相关（风险比为 0.40[95%置信区间（CI），0.19-0.83]，P=0.014）。在中位随访 24.5 个月时，12 个月无进展生存率为 21.9%（中位总生存时间为 20.9 个月[95%CI，16.6-29]，中位无进展生存时间为 8.4 个月[95%CI，7.4-9.3]）。