Real-world outcomes of regorafenib combined with immune checkpoint inhibitors in patients with advanced or metastatic microsatellite stable colorectal cancer: A multicenter study.

Abstract

BACKGROUND:

Treatment strategies are limited for patients with chemotherapy refractory microsatellite stable (MSS) colorectal cancer. We aim to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with regorafenib in this population in routine clinical practice.

METHODS:

We retrospectively analyzed patients with advanced or metastatic colorectal cancer who received at least one dose of ICIs combined with regorafenib in 14 Chinese medical centers. The primary outcome was objective response rate (ORR). This study was registered at ClinicalTrials.gov on February 2020 (NCT04771715).

RESULTS:

Eighty-four patients received ICIs combined with regorafenib from January 2019 to January 2021. Most patients (91%) received two or more systemic treatment lines before the study treatment. Seventy-six patients (90%) had confirmed MSS status. At a median follow-up of 5.5 months, four patients achieved partial response (5%) and 37 patients achieved stable disease (45%) as the best response. The median progression-free survival (PFS) was 3.1 months, and the median overall survival was 17.3 months. Eleven patients (13%) remained progression-free for more than 6 months. Baseline liver metastasis (HR 1.98, 95%CI 1.07-3.69, P = 0.03) and neutrophil-lymphocyte ratio (NLR) of ≥ 1.5 (HR 2.83, 95%CI 1.00-7.98, P = 0.05) were associated with shorter PFS in multivariate analysis. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 16 patients (19%).

CONCLUSION:

The combination of ICIs with regorafenib can be a valuable treatment option for a proportion of patients with chemotherapy refractory MSS colorectal cancer. Patients with no liver metastasis and a low NLR at baseline may derive most benefit from this strategy.

• Authors: Kaili Yang, Lu Han, Shikai Wu, Xiujuan Qu, Qin Li, Chuanhua Zhao, Jing Zhou, Xuan Jin, Yusheng Wang, Dong Yan, Zhiqiang Cheng, Yuwei Hua, Yan Zhang, Yang Ge, Jinghua Sun, Wei Deng, Lin Zhao, Yunbo Zhao
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 71 Issue 6 Pg. 1443-1451 (Jun 2022) ISSN: 1432-0851 [Electronic] Germany
• PMID: 34689233 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2021. The Author(s).

Chemical References

• Immune Checkpoint Inhibitors
• Phenylurea Compounds
• Pyridines
• regorafenib

Topics

• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Liver Neoplasms (drug therapy)
• Microsatellite Repeats
• Phenylurea Compounds (therapeutic use)
• Pyridines
• Retrospective Studies