Abstract
BackgroundMicrosatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. However, a recent Japanese trial showed that regorafenib plus nivolumab had encouraging anti-cancer activity in MSS or pMMR mCRCs.Materials and MethodsWe retrospectively reviewed the efficacy and safety data of combination therapy with regorafenib plus anti-PD-1 antibody in patients with refractory MSS or pMMR mCRC in the medical centers of Shandong Province in China.ResultsTwenty-three patients with MSS or pMMR mCRC received regorafenib plus anti-PD-1 antibody. Eighteen (78.3%) patients experienced stable disease as best response, five (21.7%) patients had progressive disease, and no partial response was observed. The disease control rate (DCR) was 78.3% (18/23), and the median progression-free survival (PFS) was 3.1 months (95% CI, 2.32-3.89). Four of five (80.0%) patients with progressive disease had baseline liver metastasis, while nine of 18 (50.0%) patients with stable disease displayed no liver metastasis. One patient receiving radiofrequency ablation treatment for liver and abdominal wall metastases prior to combination treatment experienced a remarkably prolonged PFS of 9.2 months with SD. Neither liver metastasis status nor previous exposure to regorafenib was associated with treatment outcome. Treatment-related grade 3 toxicities were observed in 5/23 (21.7%) patients.ConclusionNo objective response was observed with the combination of regorafenib plus anti-PD-1 antibody, suggesting its little clinical activity in unselected Chinese patients with pMMR/MSS mCRC. Meanwhile, it exhibited some potential benefit in this cohort in terms of DCR and PFS. Adverse events were generally tolerable and manageable. Prospective studies with large sample sizes are needed to verify the findings. This combination strategy plus local ablative therapy might be worthy of further exploration.
Highlights
Immune checkpoint inhibitors (ICIs), including antiprogrammed death-1 (PD-1), anti-programmed death ligand-1 (PD-L1), and anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)antibodies have improved overall survival (OS) of patients with multiple types of malignancies, including melanoma, renal cancer, and non-small cell lung cancer [1, 2]
A recent Canadian study demonstrated that combination of PD-L1 and CTLA-4 inhibitors could be potentially effective in a minority group of patients with pMMR/microsatellite stable (MSS) tumors, alternative strategies modulating the cold immune microenvironment were required for this major metastatic colorectal cancer (mCRC) subtype [8, 9]
We carried out a retrospective study of patients with pMMR/ MSS mCRC treated in the medical centers of Shandong Province in China receiving an anti-PD-1 antibody combined with regorafenib as third or later line treatment for a compassionate purpose
Summary
Immune checkpoint inhibitors (ICIs), including antiprogrammed death-1 (PD-1), anti-programmed death ligand-1 (PD-L1), and anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)antibodies have improved overall survival (OS) of patients with multiple types of malignancies, including melanoma, renal cancer, and non-small cell lung cancer [1, 2]. PD-1/PDL1 blockade immunotherapy failed in the microsatellite stable (MSS) or mismatch repair proficient (pMMR) mCRC subgroup, which constituted the majority of mCRC patients [5]. A recent Canadian study demonstrated that combination of PD-L1 and CTLA-4 inhibitors could be potentially effective in a minority group of patients with pMMR/MSS tumors, alternative strategies modulating the cold immune microenvironment were required for this major mCRC subtype [8, 9]. A recent Phase Ib study reported early evidence of the efficacy of regorafenib plus nivolumab with an objective response rate of 33% and a prolonged median progression-free survival of more than 6 months in 24 Asian patients with pMMR/MSS refractory mCRC [10]. Microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) is resistant to immune checkpoint inhibitors. A recent Japanese trial showed that regorafenib plus nivolumab had encouraging anti-cancer activity in MSS or pMMR mCRCs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
