联合药物化疗和抗表皮生长因子受体（EGFR）抗体被认为是RAS野生型和左侧转移性结直肠癌（mCRC）的一线治疗方案，而二线治疗方案尚未确立。目前为数不多的研究在野生型RAS mCRC的一线抗EGFR抗体治疗后前瞻性评估了抗血管内皮生长因子抗体的二线治疗。这个非随机分组的二期临床试验调查了RAS野生型mCRC患者在一线抗EGFR抗体联合双重或三重方案治疗后接受二线拉莫西单抗（RAM）联合氟尿嘧啶、左旋、伊立替康（FOLFIRI）的临床结果。主要终点是6个月无进展生存率（PFS）。次要终点包括PFS、总生存率（OS）、客观缓解率（ORR）、早期肿瘤缩小率（ETS）和安全性。我们假设6个月PFS率的阈值为30％，预期的6个月PFS率为45％。如果6个月PFS率的90％置信区间（CI）的下限大于0.30，则认为治疗有效.本研究纳入了92名患者。86（95.6％）名患者的原发肿瘤位于左侧。20（22.0％）名患者曾接受三重方案加氨甲喋呤作为前期治疗。6个月PFS率为58.2％（90％CI 49.3％至66.2％），中位PFS为7.0个月（95％CI 5.7-7.6个月）。中位OS为23.6个月（95％CI 16.5-26.3个月）。83名可测量病变的患者中，ORR和ETS率分别为10.7％和16.9％。以前接受双重和三重方案治疗的患者的6个月PFS率相当；然而，双重方案的中位PFS时间较长（7.4 vs 6.4个月，P = 0.036）。我们的研究前瞻性地证实，对野生型RAS和左侧mCRC抗EGFR抗体一线治疗之后，RAM加FOLFIRI是有效的二线治疗。此外，先前接受三重方案治疗的患者的结果与之类似。版权所有©2023作者。由Elsevier Ltd.出版。保留所有权利。

Chemotherapy in combination with anti-epidermal growth factor receptor (EGFR) antibody is considered a first-line treatment regimen for RAS wild-type and left-sided metastatic colorectal cancer (mCRC), whereas second-line treatment regimens have not yet been established. Few studies have prospectively evaluated second-line treatment with anti-vascular endothelial growth factor antibody after first-line anti-EGFR antibody therapy for RAS wild-type mCRC.This non-randomized phase II trial investigated the clinical outcomes of second-line ramucirumab (RAM) plus fluorouracil, levofolinate, and irinotecan (FOLFIRI) after first-line anti-EGFR antibody in combination with doublet or triplet regimen in patients with RAS wild-type mCRC. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were PFS, overall survival (OS), objective response rate (ORR), rate of early tumor shrinkage (ETS), and safety. We hypothesized a threshold 6-month PFS rate of 30% and an expected 6-month PFS rate of 45%. Treatment was considered effective if the lower limit of the 90% confidence interval (CI) of the 6-month PFS rate was >0.30.Ninety-two patients were enrolled in the study. The primary tumor was located on the left side in 86 (95.6%) patients. Twenty (22.0%) patients had received triplet plus cetuximab as previous therapy. Six-month PFS rate was 58.2% (90% CI 49.3% to 66.2%) with a median PFS of 7.0 months (95% CI 5.7-7.6 months). Median OS was 23.6 months (95% CI 16.5-26.3 months). The ORR and ETS rate were 10.7% and 16.9%, respectively, in 83 patients with measurable lesions. The 6-month PFS rate was comparable between patients previously treated with doublet and triplet regimens; however, median PFS was longer for the doublet regimen (7.4 versus 6.4 months, P = 0.036).Our study demonstrated prospectively that RAM plus FOLFIRI is an effective second-line treatment after anti-EGFR antibody-containing first-line therapy in RAS wild-type and left-sided mCRC. Furthermore, the results were similar for patients who were previously treated with triplet regimen.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.