mFOLFOX6+Bevacizumab+PD-1 Monoclonal Antibody in Local Advanced MSS CRC

Summary

Immunotherapy has achieved significant therapeutic effect in DNA mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, for proficient mismatch repair(pMMR)/microsatellite stable(MSS) CRC, the curative effect of PD-1 monoclonal antibody was poor and most of the data came from stage Ⅳ patients with distant metastasis. Among the whole CRC patients, more than eighty-five percent were pMMR/MSS CRC. It would be very inspiring when major CRC patients(pMMR/MSS) could be benefit from immunotherapy. For T4NxM0 CRC patients, R0 resection was difficult to achieve. If the patients could not got R0 resection, which means the tumors were almost destined to recurrent and patients life time were counting down. Whether combined treatment of mFOLFOX6+ Bevacizumab+PD-1 monoclonal antibody could maximize the curative effect was still unknown. This study aims to evaluate the effect and safety of mFOLFOX6+ Bevacizumab+PD-1 monoclonal antibody treatment combinations in patients with local advanced(T4NxM0) pMMR/MSS CRC.

Timeline

Start

2021-05-01

Primary completion

2024-09-30

Completion

2024-09-30

Publications

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• Results Kim SA, Kim JW, Suh KJ, Chang W, Kim JW, Oh HK, Cho JY, Kim DW, Cho S, Kim JH, Kim K, Kang SB, Jheon S, Lee KW. Conversion surgery after cetuximab or bevacizumab plus FOLFIRI chemotherapy in colorectal cancer patients with liver- and/or lung-limited metastases. J Cancer Res Clin Oncol. 2020 Sep;146(9):2399-2410. doi: 10.1007/s00432-020-03233-7. Epub 2020 May 1.
• Results Li J, Cong L, Liu J, Peng L, Wang J, Feng A, Yue J, Li L, Wang X, Wang X. The Efficacy and Safety of Regorafenib in Combination With Anti-PD-1 Antibody in Refractory Microsatellite Stable Metastatic Colorectal Cancer: A Retrospective Study. Front Oncol. 2020 Nov 12;10:594125. doi: 10.3389/fonc.2020.594125. eCollection 2020.
• Results Marmorino F, Boccaccino A, Germani MM, Falcone A, Cremolini C. Immune Checkpoint Inhibitors in pMMR Metastatic Colorectal Cancer: A Tough Challenge. Cancers (Basel). 2020 Aug 17;12(8):2317. doi: 10.3390/cancers12082317.
• Results Mise Y, Hasegawa K, Saiura A, Oba M, Yamamoto J, Nomura Y, Takayama T, Hashiguchi Y, Shibasaki M, Sakamoto H, Yamagata S, Aoyanagi N, Kaneko H, Koyama H, Miyagawa S, Shinozaki E, Yoshida S, Nozawa H, Kokudo N. A Multicenter Phase 2 Trial to Evaluate the Efficacy of mFOLFOX6 + Cetuximab as Induction Chemotherapy to Achieve R0 Surgical Resection for Advanced Colorectal Liver Metastases (NEXTO Trial). Ann Surg Oncol. 2020 Oct;27(11):4188-4195. doi: 10.1245/s10434-020-08627-y. Epub 2020 Jun 8.
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• Results Yuan Y, Xiao WW, Xie WH, Cai PQ, Wang QX, Chang H, Chen BQ, Zhou WH, Zeng ZF, Wu XJ, Liu Q, Li LR, Zhang R, Gao YH. Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection. BMC Cancer. 2021 Feb 19;21(1):179. doi: 10.1186/s12885-021-07894-6.

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Indications