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.

Comparison of the efficacy and safety of fruquintinib and regorafenib in the treatment of metastatic colorectal cancer: A real-world study

“…39 patients who received regorafenib combined with toripalimab, with a median PFS of 2.6 months, a median OS of 15.5 months, and an ORR of 15.2% (24). Another multicenter retrospective study of regorafenib combined with immune checkpoint inhibitors included 84 mCRC patients, with an ORR of 5% and a median PFS of 3.1 months (25). Obviously, our results are similar to those of the appeal study in China.…”

The prognostic role of neutrophil-to-lymphocyte ratio and C-reactive protein in metastatic colorectal cancer using regorafenib: a systematic review and meta-analysis

“…The 3 references retrieved by citation were excluded because they were all from the same clinical trial and did not report detailed data on outcome indicators. Finally, 8 studies (14,30,31,(34)(35)(36)(37)(38) with a total of 1,287 patients were included in the metaanalysis (Table 1). The NOS scores of the included studies were all ≥7 (Table 2), indicating that the quality of the studies was good.…”

Regorafenib with or without a programmed cell death protein 1 antibody as third‐line treatment for microsatellite stable metastatic colorectal cancer

“… 5 However, several other studies evaluating the same treatment strategy failed to observe such a high response rate. 6 , 7 , 8 These discrepant observations suggest that only a subset of patients may benefit from this combination. Our findings suggest that regorafenib combined with a PD‐1 antibody has similar efficacy as regorafenib monotherapy in unselected MSS mCRC as a third‐line treatment option.…”

“… 7 Yang et al conducted a study that involved 14 Chinese medical centers and reported a partial response of 5% (4/84 patients) and a median PFS of 3.1 months. 8 …”