A Phase Two Trial Evaluating FOLFIRI Plus Aflibercept After Failure of FOLFOXIRI Plus Bevacizumab in Patients with Unresectable Metastatic Colorectal Cancer

Overview

Journal Int J Clin Oncol

Date 2025 Feb 1

PMID 39891883

Authors

Koji Ando

Hironaga Satake

Mototsugu Shimokawa

Hisateru Yasui

Yuji Negoro

Tatsuya Kinjo

Junya Kizaki

Kenji Baba

Hiroyuki Orita

Keiji Hirata

Sanae Sakamoto

Akitaka Makiyama

Hiroshi Saeki

Akihito Tsuji

Hideo Baba

Eiji Oki

Affiliations

Soon will be listed here.

Abstract

Background: FOLFOXIRI plus bevacizumab (BEV) is an option for first-line treatment of metastatic colorectal cancer (mCRC). However, there is no consensus on the optimal treatment strategy when disease progresses. The EFFORT open-label, multicenter, single-arm phase II study investigated whether FOLFIRI plus aflibercept retains activity after progression of FOLFOXIRI plus BEV treatment.

Methods: The patients with unresectable mCRC who failed first-line FOLFOXIRI plus BEV received FOLFIRI plus aflibercept. The primary endpoint was progression-free survival (PFS) in the full analysis set (FAS). Angiogenic biomarkers were measured before treatment initiation.

Results: From April 2019 to May 2021, 35 patients were enrolled and 34 were analysed in the FAS population (men, 18; median age, 63 years [range: 32-78]). The primary tumor was left-sided in most cases (23/34), 23 patients were RAS mutant, 3 patients had BRAF V600E mutation and 27 patients had liver metastases. The primary end-point was met with a median PFS of 4.3 months [80% confidence interval [CI] 3.7-5.1]. Median overall survival was 15.2 months [95% CI 8.9-22.7]. Per RECIST, there were 1 complete response, 4 partial responses, 21 stable diseases and 8 disease progressions. Overall response rate was 14.7% [95% CI 5.0-31.1], and disease control rate was 76.5% [95% CI 58.8-89.3]. Responses were more common in patients with high VEGF-C, low VEGF-D and low PlGF levels before treatment.

Conclusion: FOLFIRI plus aflibercept, administered after failure of FOLFOXIRI plus BEV, is effective and has a manageable safety profile. This regimen may be a useful second-line treatment option for these patients.

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