| Background and Objectives:With the increasing incidence and mortality,colorectal cancer(CRC)has become the most common malignant tumor in the digestive system.Metastasis is the main cause of CRC-related death.At present,the third-and later-line treatment schemes for metastatic colorectal cancer are limited.Regorafenib is an oral small-molecule multi-kinase inhibitor,which can effectively block several protein kinases involved in tumor angiogenesis,tumorigenesis,tumor metastasis and tumor immunity,and it can improve the progression free survival(PFS)and overall survival(OS)of refractory mCRC patients.However,there is limited evidence in the real world of regorafenib and its different combination medication strategies.The albumin to alkaline phosphatase ratio(AAPR)is a novel prognostic index that holds significant prognostic value in various types of cancer.Therefore,this study aimed to explore the efficacy and safety of regorafenib as the third-and later-line treatment for mCRC in the real world practice,to compare and analyze the efficacy of different combination medication strategies of regorafenib,and to explore the factors affecting the prognosis of regorafenib.Methods:This study analyzed the metastatic colorectal cancer patients who met the inclusion and exclusion criteria and accepted regorafenib as the third-and later-line treatment from December 2018 to January 2022at Henan Provincial People’s Hospital.In this study,the clinical data of patients and the related data of regorafenib were collected.According to the regimen of combination therapy of regorafenib,the patients were divided into three groups:regorafenib monotherapy group(monotherapy group),regorafenib combined immunotherapy group(immunotherapy group)and regorafenib combined chemotherapy group(chemotherapy group).The primary endpoint was OS,and the secondary endpoints were PFS and DCR.The SPSS 21.0 software was used for statistical analysis.The Pearson chi-square test or Fisher’s exact test were used to compare clinical characteristics,DCR,and adverse events among different groups.The Kaplan-Meier method was used to plot survival curves and conduct univariate analysis,with the log-rank test used to compare differences between groups.The Cox proportional hazards regression model was used for multivariate analysis.All tests were bilateral,and P<0.05 was considered statistically significant.When conducting pairwise comparisons among three groups with significant differences,a Bonferroni correction was applied with a adjusted significance level of 0.0167,meaning that P<0.0167 was considered statistically significant.Results:1.In this study,a total of 85 patients with mCRC were finally included after case screening.The median overall survival(m OS)was 10.3 months(95%CI:7.1–13.5),and the median progression free survival(m PFS)was 3.1 months(95%CI:2.4–3.8).The ORR was 1.1%and the DCR was 37.6%.2.Of all patients,there were 36 in the monotherapy group,38 in the immunotherapy group and 11 in the chemotherapy group.The m OS of the three groups were 8.2 months(95%CI:5.6–10.8),10.3 months(95%CI:5.0–15.6)and 13.8 months(95%CI:2.1–25.4)respectively,with no statistical significance(P=0.162).The m PFS of the three groups were 2.8 months(95%CI:1.2–4.4),3.4 months(95%CI:2.5–4.3)and 3.1 months(95%CI:1.6–4.6)respectively,and the difference was not statistically significant(P=0.791).The DCR of the three groups were 25%,52.6%and 27.3%respectively,and the difference was statistically significant(c~2=6.592,P=0.037).The results of pairwise comparisons showed that the DCR in the immunotherapy group was higher than that in the monotherapy group,and the difference was statistically significant(c~2=5.923,P=0.015<0.0167).3.The results of univariate analysis of OS showed that presence of liver metastasis,absence of lung metastasis,short time from diagnosis of metastasis to the start of regorafenib,previous use of bevacizumab,pre-treatment CA199>35U/L,and pre-treatment ratio of albumin to alkaline phosphatase(AAPR)≤0.42were all significantly associated with shorter OS(all P<0.05).Multivariate analysis showed that lung metastasis was an independent influencing factor of OS.Patients with lung metastasis had a 56.9%lower risk of death compared to those without lung metastasis(HR:0.431,95%CI:0.233-0.798,P=0.007).4.The results of univariate analysis of PFS showed that age,sex,primary tumor location,status of primary tumor,ECOG score,occurrence of metastasis at diagnosis,number of organs with metastasis,liver metastasis,lung metastasis,lymph node metastasis,time from metastasis to regorafenib treatment,lines of treatment,prior treatment,follow-up treatment,initial dose and final daily dose of regorafenib were not correlated with PFS(P>0.05).5.The incidence of any level of adverse events in all patients was 77.6%,among which 17 were hand-foot syndrome(21.2%),13 were appetite change(15.3%),10 were fatigue(11.8%)and 10 were abnormal liver functions(11.8%).The incidence of grade 3-4 adverse events was 10.6%.6.The incidence of any level of adverse events in monotherapy group,immunotherapy group and chemotherapy group were 75%,76.3%and 100%,respectively,with no statistical significance(P=0.212).The incidence of grade 3-4 adverse events in the three groups were 11.1%,10.5%and 0,respectively,with no statistical significance(P=0.766).Conclusion:1.This study demonstrated that regorafenib as the third-and later-line treatment for mCRC was safe and effective in the real world practice.2.The DCR of regorafenib combined with immunotherapy group was better than that of the monotherapy group.Additionally,regorafenib combined with immunotherapy or chemotherapy had a certain trend of survival benefit than regorafenib monotherapy.However,further studies with larger sample sizes were needed to compare the efficacy of different combination strategies.3.This study also demonstrated that presence of liver metastasis,absence of lung metastasis,short time from diagnosis of metastasis to the start of regorafenib,prior use of bevacizumab,pre-treatment CA199 levels>35U/L,and pre-treatment AAPR≤0.42 were all poor prognosis factors for mCRC patients who have received third-and later-line treatment with regorafenib.4.The multivariate analysis indicated that lung metastasis was an independent factor that positively affects the prognosis of third-and later-line treatment for mCRC with regorafenib. |
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