FOLFIRI联合雷莫西尤单抗治疗对奥沙利铂/氟嘧啶辅助化疗耐药的复发性结直肠癌的疗效——包括生物标志物分析

The Efficacy of FOLFIRI Plus Ramucirumab in Recurrent Colorectal Cancer Refractory to Adjuvant Chemotherapy with Oxaliplatin/Fluoropyrimidine-Including Biomarker Analyses.

作者信息

Sugimoto Naotoshi, Noura Shingo, Kato Takeshi, Yoshioka Shinichi, Hata Taishi, Naito Atsushi, Tei Mitsuyoshi, Tamagawa Hiroshi, Komori Takamichi, Ide Yoshihito, Fukuzaki Takayuki, Danno Katsuki, Sawada Genta, Kagawa Yoshinori, Shimokawa Toshio, Miyoshi Norikatsu, Ogino Takayuki, Uemura Mamoru, Yamamoto Hirofumi, Murata Kohei, Doki Yuichiro, Eguchi Hidetoshi

机构信息

Department of Genetic Oncology, Osaka International Cancer Institute, Osaka 5418567, Japan.

Department of Surgery, Sakai City Medical Center, Sakai 5938304, Japan.

出版信息

Cancers (Basel). 2024 Dec 30;17(1):91. doi: 10.3390/cancers17010091.

DOI:10.3390/cancers17010091

PMID:39796720

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11719561/

Abstract

BACKGROUND

FOLFIRI (5-FU + leucovorin + irinotecan) plus ramucirumab is one of the standards in second-line metastatic colorectal cancer (CRC) patients progressing after treatment with oxaliplatin/fluoropyrimidine with bevacizumab, but there is no evidence on its efficacy without prior bevacizumab. Moreover, VEGF-D has not been confirmed as a predictive biomarker for ramucirumab's efficacy, either.

METHODS

The RAINCLOUD study was a multicenter, single-arm, phase II trial conducted in Japan. Patients with recurrent CRC pretreated with fluoropyrimidine and oxaliplatin without bevacizumab were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints measured were overall survival (OS), overall response rate (ORR), and safety.

RESULTS

A total of 48 patients were enrolled from 15 sites between September 2017 and September 2020. Their median age was 63.5 years (25~77), 20.1% had a right-sided tumor, and 68.8% had -mutant cancer. The median PFS was 8.9 months (90% CI: 6.3-11.8), so the primary endpoint was met. Their median OS and ORR were 22.3 months (95% CI: 17.4-NA) and 41.7% (95% CI: 4.9-7.6), respectively. An incidence of grade 3/4 adverse events that reached over 5% applied to neutropenia (44%), leucopenia (10%), and hypertension (8%). In the biomarker analysis, the serum VEGF-D levels post-treatment were higher than those pre-treatment, but the PFS in those with high VEGF-D levels trended towards being worse than that in those with low VEGF-D (7.6M/5.6M ( = 0.095; HR: 0.56)). Instead, those with low TSP-2 had a better PFS than those with high TSP-2 (7.5M/4.3M ( = 0.022; HR: 0.45)).

CONCLUSIONS

Our data suggested that FOLFIRI plus ramucirumab was effective and tolerable for CRC refractory to fluoropyrimidine and oxaliplatin without anti-angiogenesis. Serum VEGF-D levels may not be predictive but TSP-2 may be a potential prognostic biomarker for ramucirumab's efficacy.

摘要

背景

FOLFIRI（5-氟尿嘧啶+亚叶酸钙+伊立替康）联合雷莫西尤单抗是二线转移性结直肠癌（CRC）患者在接受奥沙利铂/氟嘧啶联合贝伐单抗治疗后病情进展的标准治疗方案之一，但尚无证据表明其在未使用过贝伐单抗的情况下的疗效。此外，血管内皮生长因子-D（VEGF-D）也未被确认为雷莫西尤单抗疗效的预测生物标志物。

方法

RAINCLOUD研究是在日本进行的一项多中心、单臂、II期试验。对未使用贝伐单抗接受氟嘧啶和奥沙利铂预处理的复发性CRC患者进行分析。主要终点是无进展生存期（PFS）。测量的次要终点包括总生存期（OS）、总缓解率（ORR）和安全性。

结果

2017年9月至2020年9月期间，共有48例患者从15个研究点入组。他们的中位年龄为63.5岁（25~77岁），20.1%的患者肿瘤位于右侧，68.8%的患者患有 -突变癌。中位PFS为8.9个月（90%CI：6.3-11.8），因此达到了主要终点。他们的中位OS和ORR分别为22.3个月（95%CI：17.4-NA）和41.7%（95%CI：4.9-7.6）。发生率超过5%的3/4级不良事件包括中性粒细胞减少（44%）、白细胞减少（10%）和高血压（8%）。在生物标志物分析中，治疗后血清VEGF-D水平高于治疗前，但VEGF-D水平高的患者的PFS有比VEGF-D水平低的患者更差的趋势（7.6个月/5.6个月（ = 0.095；HR：0.56））。相反，血小板反应蛋白-2（TSP-2）水平低的患者的PFS比TSP-2水平高的患者更好（7.5个月/4.3个月（ = 0.022；HR：0.45））。