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

Abstract

Although the use of regorafenib plus nivolumab demonstrates promising outcomes in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC), other studies failed to observe such an effect. In addition, a comparison between regorafenib combined with programmed cell death protein 1 (PD-1) antibodies and regorafenib monotherapy has rarely been reported. The aim of this study was to assess whether regorafenib combined with a PD-1 antibody is superior to regorafenib monotherapy as third-line treatment for MSS mCRC. MethodsPatients with MSS mCRC who received regorafenib combined with a PD-1 antibody or regorafenib monotherapy as third-line treatment were eligible for inclusion. ResultsIn total, 179 patients were enrolled, of which 95 administered regorafenib combined with a PD-1 antibody and 84 administered regorafenib monotherapy. Overall, patients who administered regorafenib combined with a PD-1 antibody had similar progression-free survival (PFS) outcomes as those on regorafenib monotherapy (median PFS was 2.4 months and 1.9 months, respectively, P = 0.086). The administration of regorafenib combined with a PD-1 antibody showed signi cantly longer PFS than regorafenib monotherapy in both male (5.2 months vs. 2.4 months, P = 0.001) and female (3.9 months vs. 1.8 months, P = 0.037) patients without liver metastasis. Unexpectedly, female patients with liver metastasis who administered regorafenib combined with a PD-1 antibody showed inferior PFS outcomes than those who administered regorafenib monotherapy (1.8 months vs. 2.0 months, P = 0.030). ConclusionLiver metastasis and gender were predictors of survival bene t following the addition of a PD-1 antibody to regorafenib in patients with MSS mCRC.

Regorafenib in patients with pretreated advanced melanoma: a single-center case series

“…Our retrospective analysis of the clinical outcome of 27 pretreated advanced melanoma patients who were treated with REGO (including monotherapy and combination strategies) represents, to the best of our knowledge, the first experience with this multitargeted kinase inhibitor in this specific patient population. The interest to explore the potential therapeutic activity of REGO in advanced melanoma was sparked by results suggesting that REGO could overcome resistance to anti-PD-1 checkpoint blockade in immunotherapy refractory cancers such as mismatch repair proficient (microsatellite stable) colorectal cancer and gastric cancers [26][27][28][29]. Potential synergy between REGO and PD-1/-ligand-1targeted immune therapy has also been suggested for melanoma [30].…”

Efficacy comparison of fruquintinib, regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer

“…In patients with an ECOG score of 0-1, the OS of the RP group was even worse than that of the R group. In a retrospective study, He et al [ 26 ] indicated that there was no significant difference between the combination therapy group (RP) and the R group in the median PFS (2.4 months vs 1.9 months, P > 0.05). In female patients with liver metastasis who were administered R combined with a PD-1 antibody even had a shorter PFS than those administered R monotherapy (1.8 vs 2.0 months, P = 0.030)[ 26 ].…”

“…In a retrospective study, He et al [ 26 ] indicated that there was no significant difference between the combination therapy group (RP) and the R group in the median PFS (2.4 months vs 1.9 months, P > 0.05). In female patients with liver metastasis who were administered R combined with a PD-1 antibody even had a shorter PFS than those administered R monotherapy (1.8 vs 2.0 months, P = 0.030)[ 26 ]. In our study, there was also no evidence that the RP regimen could bring a significant survival benefit to patients compared with R. RP even increased the incidence of some adverse reactions, leading to discontinuation of medication or a decline in physical status in some patients, which may affect patients survival.…”

RNA Expression-Based Analysis to Predict Response in Patients with Metastatic Mismatch Repair Proficient Colorectal Cancer Treated with Regorafenib and Nivolumab

“…Identification of biomarkers that predict treatment benefit may assist in se-lecting patients for this strategy. Previous studies have linked liver metastasis, cytotoxic T cells, Tregs, tumorassociated macrophages, plasma levels of biomarkers of vascular biology, circulating tumor DNA, neutrophil-tolymphocyte ratio, gut microbiome, etc., with treatment response [6,9,10,[12][13][14][15]. However, predictive biomarkers for anti-angiogenesis and immunotherapies have been challenged by the limited studies and the inconsistent results.…”

“…The combination of regorafenib with PD-1 targeting for patients with refractory CRC has been evaluated in both prospective and retrospective settings [4][5][6][7][8][9][10][11][12][13][14][15]. The treatment efficacy in different studies among different patient populations varies greatly.…”