A Phase II Study of FOLFIRI Plus Ziv-Aflibercept After Trifluridine/Tipiracil Plus Bevacizumab in Patients with Metastatic Colorectal Cancer: WJOG 11018G

• Published in: Targeted oncology Vol. 19; no. 2; pp. 181 - 190
• Main Authors: Matsumoto, Toshihiko, Yamamoto, Yoshiyuki, Kotaka, Masahito, Masuishi, Toshiki, Tsuji, Yasushi, Shoji, Hirokazu, Hirata, Kenro, Tsuduki, Takao, Makiyama, Akitaka, Izawa, Naoki, Takahashi, Naoki, Tsuda, Masahiro, Yasui, Hisateru, Ohta, Takashi, Kito, Yosuke, Otsu, Satoshi, Hironaka, Shuichi, Yamazaki, Kentaro, Boku, Narikazu, Hyodo, Ichinosuke, Yoshimura, Kenichi, Muro, Kei
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2024; Springer Nature B.V
• Subjects: Biomarkers; Biomedicine; Colorectal cancer; Growth factors; jRCTs; jRCTs041190100; Medicine; Medicine & Public Health; Metastasis; Oncology; Original; Original Research Article
• ISSN: 1776-2596; 1776-260X
• DOI: 10.1007/s11523-024-01043-2

Background Non-inferiority of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) to irinotecan/fluoropyrimidine plus BEV in metastatic colorectal cancer was investigated in the phase III TRUSTY study, and we conducted a phase II study of FOLFIRI (5-FU+leucovorin+irinotecan) plus zib-aflibercept (AFL) after FTD/TPI plus BEV. However, the TRUSTY study failed during the recruitment of our patients. Objective We present the findings of a phase II study on the efficacy of FOLFIRI plus zib-aflibercept (AFL) after FTD/TPI plus BEV, including clinical results with plasma biomarker analyses. Methods This was a multicenter, single-arm, phase II study in patients with metastatic colorectal cancer refractory or intolerant to oxaliplatin, fluoropyrimidine, BEV, and FTD/TPI. The primary endpoint was progression-free survival. Fifteen plasma angiogenesis-associated biomarkers were analyzed using a Luminex ® multiplex assay U-kit. Results Between January 2020 and May 2022, 26 patients (median age, 68 years) from 15 sites were enrolled. The median progression-free survival was 4.9 months (85% confidence interval, 3.4 month–not estimated). The overall response and disease control rates were 8% and 62%, respectively. The median levels of vascular endothelial growth factor-A and placental growth factor, both targets of AFL, were below the measurable limit of 30 pg/mL and 16 pg/mL, respectively. Patients were divided into two groups at the median levels of baseline biomarkers. The progression-free survival did not differ between high and low expressers of placental growth factor ( p = 0.7), while it tended to be shorter in those with high levels of osteopontin ( p = 0.05), angiopoietin-2 ( p = 0.07), and tissue inhibitor of matrix metalloproteinases-1 ( p = 0.1). Conclusions This study did not meet the primary endpoint. Hence, FOLFIRI plus AFL should not be used after FTD/TPI plus BEV for metastatic colorectal cancer. Further studies are needed to determine factors not targeted by AFL that may affect the efficacy of the treatment. Clinical Trial Registration jRCTs041190100.