A meta-analysis comparing regorafenib with TAS-102 for treating refractory metastatic colorectal cancer

Objective We performed this meta-analysis to compare the efficacy and toxicity of regorafenib and TAS-102. Methods Electronic databases were searched to identify studies comparing the efficacy and safety of regorafenib and TAS-102 in patients with chemotherapy-refractory metastatic colorectal cancer using pooled analyses. Results Three clinical trials were included in this analysis. Regarding the reasons for treatment discontinuation, regorafenib was significantly associated with disease progression (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.21–0.50) and adverse events (OR = 4.38, 95% CI = 2.69–7.13). However, overall (OR = 0.97, 95% CI = 0.81–1.17) and progression-free survival (OR = 1.01, 95% CI = 0.86–1.18) did not significantly differ between the groups. The most common treatment-related adverse events in the regorafenib group were neutropenia (OR = 0.06, 95% CI = 0.03–0.11), hand–foot syndrome (OR = 50.34, 95% CI = 10.44–242.84), and liver dysfunction (OR = 34.51, 95% CI = 8.30–143.43). Conversely, the incidence of thrombocytopenia did not differ between the two groups. Conclusions Regorafenib and TAS-102 have similar efficacy but different adverse event profiles. Differences in the toxicity profiles of the two drugs will help guide treatment selection.

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TAS-102 Independent and Combined Therapy in Metastatic Colorectal Cancer

10.21203/rs.3.rs-735929/v1 ◽

2021 ◽

Author(s):

Cheng-Jiang Liu ◽

Ting Hu ◽

Ping Shao ◽

Wu-Yang Chu ◽

Yu Cao ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Treatment Plan ◽

Combined Therapy ◽

Meta Analysis ◽

Combined Treatment ◽

Progression Free Survival ◽

Cochrane Library ◽

Free Survival

Abstract Objective To evaluate the effectiveness and safety of TAS-102 in the treatment of metastatic colorectal cancer. Methods The pubmed, web of science, medline, cochrane library databases were searched for the literature on TAS-102 treatment of metastatic colorectal cancer. Extract data such as median Overall Survival (mOS), median Progression-Free Survival (mPFS) and the incidence of adverse events for meta-analysis. Results Our study found that the mOS of patients treated with TAS-102 was 7.74 (95%CI: 6.09–9.85) and the mPFS was 2.91 (95%CI: 2.38–3.57). The mOS in patients treated by TAS-102 Combined with bevacizumab is 10.41 (95%CI: 8.40-12.89) and the mPFS is 4.35 (95%CI: 3.05–6.20). In the control experiment, the patients' mOS and mPFS were improved. TAS-102 + B VS. TAS- 102 (OR = 0.41, 95% CI: 0.18–0.93; OR = 0.72, 95% CI: 0.63–0.83). TAS-102 VS. Placebo(OR = 0.44, 95% CI: 0.29–0.67; OR = 0.51, 95% CI: 0.42–0.62). The incidence of adverse events in combination with bevacizumab will increase. Conclusion TAS-102 single or combined treatment can significantly improve the survival of patients, and drug safety should be considered when formulating a combined treatment plan.

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Systematic Review and Meta-Analysis of Multitargeted Tyrosine Kinase Inhibitors in Patients With Intractable Metastatic Colorectal Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033820943241 ◽

2020 ◽

Vol 19 ◽

pp. 153303382094324

Author(s):

Zhenzhen Gao ◽

Chenxi Cao ◽

Yi Bao ◽

Yaohua Fan ◽

Gang Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Network Analysis ◽

Confidence Interval ◽

Metastatic Colorectal Cancer ◽

Odds Ratio ◽

Meta Analysis ◽

Progression Free Survival ◽

Controlled Trials ◽

Free Survival

Background: The treatment options for intractable metastatic colorectal cancer include regorafenib, trifluridine/tipiracil, and fruquintinib. In this study, we aimed to conduct a network meta-analysis for comparing the efficacy of these agents. Methods: We searched the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials databases for relevant literature, up to February 2020. The data were collected from randomized controlled trials on regorafenib, trifluridine/tipiracil, or fruquintinib, administered to patients with metastatic colorectal cancer who failed on treatment with oxaliplatin, irinotecan, or fluoropyrimidine. The primary end points, namely, the overall survival and progression-free survival, were analyzed for subsequent network analysis using the Review Manager and Aggregate Data Drug Information System software for performing direct and indirect comparisons. Results: A total of 7 trials were analyzed in this study. Trifluridine/tipiracil and regorafenib proved to be superior to the placebo, with respect to the overall survival (odds ratio: 0.38, 95% confidence interval: 0.27-0.52 for trifluridine/tipiracil; odds ratio: 0.47, 95% confidence interval: 0.26-0.84 for regorafenib) and progression-free survival (odds ratio: 0.18, 95% confidence interval: 0.05-0.67 for trifluridine/tipiracil; odds ratio: 0.06, 95% confidence interval: 0.04-0.09 for regorafenib). Regorafenib (80 mg) was superior to the placebo in terms of the overall survival and progression-free survival and inferior to trifluridine/tipiracil and fruquintinib. Network analysis revealed that the efficacy of trifluridine/tipiracil and fruquintinib was fundamentally similar, and both the agents were superior to regorafenib. Conclusion: Regorafenib (80 mg) was superior to the placebo, but inferior to 160 mg regorafenib, trifluridine/tipiracil, and fruquintinib. This study further revealed that the efficiency of trifluridine/tipiracil and fruquintinib is identical, but their toxicity profiles are different.

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TAS-102 Monotherapy and Combination Therapy with Bevacizumab for Metastatic Colorectal Cancer

Gastroenterology Research and Practice ◽

10.1155/2021/4014601 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Cheng-Jiang Liu ◽

Ting Hu ◽

Ping Shao ◽

Wu-Yang Chu ◽

Yu Cao ◽

...

Keyword(s):

Colorectal Cancer ◽

Combination Therapy ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Median Overall Survival ◽

Control Experiment ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Free Survival

Objective. To evaluate the effectiveness and safety of TAS-102 monotherapy and combination therapy with bevacizumab in the treatment of metastatic colorectal cancer. Methods. The PubMed, Web of Science, MEDLINE, and Cochrane Library databases were searched for the literature on TAS-102 treatment of metastatic colorectal cancer. Extracted data include median overall survival (mOS), median progression-free survival (mPFS), and the incidence of adverse events for meta-analysis. Results. Our study found that the mOS of patients treated with TAS-102 monotherapy was 6.95 (95% CI: 6.26-7.72) months and the mPFS was 2.53 (95% CI: 2.31-2.78) months. The mOS in patients treated by TAS-102 combined with bevacizumab was 10.41 (95% CI: 8.40-12.89) months, and the mPFS is 4.35 (95% CI: 3.05-6.20) months. In the control experiment, the patients’ mOS and mPFS were improved. TAS-102+B vs. TAS-102 ( OR = 0.41 , 95% CI: 0.18-0.93; OR = 0.72 , 95% CI: 0.63-0.83) and TAS-102 vs. placebo ( OR = 0.44 , 95% CI: 0.29-0.67; OR = 0.51 , 95% CI: 0.42-0.62) were studied to actively prevent the occurrence of neutropenia, leukopenia, febrile neutropenia, anemia, and vomiting. Conclusion. TAS-102 monotherapy and combination therapy with bevacizumab can significantly improve the survival of patients and prevent specific adverse events from happening.

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Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

Cancers ◽

10.3390/cancers12092663 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2663

Author(s):

Tung Hoang ◽

Jeongseon Kim

Keyword(s):

Colorectal Cancer ◽

Meta Analysis ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Cancer Treatments ◽

Free Survival ◽

Hazard Ratios ◽

Credible Intervals ◽

Grade 3 ◽

Selection Of

This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73–0.98; HR = 0.76, 95% CrI = 0.62–0.94; HR = 0.80, 95% CrI = 0.66–0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51–0.94 and HR = 0.73, 95% CrI = 0.54–0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01–4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09–3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51–5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.

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Reintroduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.630 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 630-630 ◽

Cited By ~ 1

Author(s):

Tohru Sasaki ◽

Mizutomo Azuma ◽

Wasaburo Koizumi ◽

Tomohisa Egawa ◽

Atsushi Nagashima ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Initial Treatment ◽

Performance Status ◽

Progression Free Survival ◽

Standard Chemotherapy ◽

Free Survival ◽

Clinical Benefits ◽

Better Than

630 Background: Reintroduction of oxaliplatin seems to have clinical benefits for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens. A interim analysis of RE-OPEN study reported 38.9% of disease control rate (DCR) in ASCO GI 2013, but it is still unknown who will receive benefits from reintroduction of oxaliplatin. Methods: Among patients in whom oxaliplatin was reintroduced in the 7 participating hospitals, we retrospectively studied patients who had previously received oxaliplatin and irinotecan and patients who had a response of stable disease or better during initial treatment with oxaliplatin. Results: From June 2009 through January 2013, oxaliplatin was reintroduced in 53 patients (31 men and 22 women). The median age was 64 years, and the performance status was 0 in 24 patients and 1 in 29. The reasons for discontinuing initial treatment with oxaliplatin were progressive disease in 36 patients, adverse events in 14 and others in 3. The response rate (RR), DCR, the median progression-free survival (PFS), and the median overall survival were 3.8%, 47.2%, 105 days, and 313 days, respectively. As for adverse events, allergic reactions to oxaliplatin (grade 1 or higher) occurred in 26% of the patients. RR, DCR, and PFS in 44 patients with the oxaliplatin-free-interval (OFI) over 6 months were 4.6%, 54.6%, and 119 days, respectively, and were statistically better than those in 9 patients with OFI less than 6 months (0%, 11.1%, and 84 days). Reintroduction of oxaliplatin with bevacizumab showed better PFS than that without bevacizumab (114 days and 78 days, respectively). Conclusions: Reintroduction of oxaliplatin was suggested to be one option for the management of colorectal cancer that is resistant to standard therapy, especially in patients with OFI over 6 months. Bevacizumab may enhance the results of reintroduction treatment.

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Efficacy and safety of regorafenib in combination with chemotherapy as second-line therapy in patients with metastatic colorectal cancer: A network meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.115 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 115-115

Author(s):

Xiaoyu Xie ◽

Jianwei Zhang ◽

Huabin Hu ◽

Yue Cai ◽

Zehua Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Biological Agents ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

R Software

115 Background: Recent studies have shown efficacy of chemotherapy (CTX) in combination with different biological agents including regorafenib (REG) in second-line treatment of metastatic colorectal cancer (mCRC). As there is no evidence on the relative efficacy and safety of REG as compared to other biological agents in combination with CTX, we evaluated the same in this network meta-analysis (NMA). Methods: Randomized controlled trials (RCTs) comparing efficacy and safety of biological agents + CTX against CTX alone as second-line treatment of mCRC were retrieved from PubMed, EMBASE and Cochrane databases. Progression free survival (PFS) was the primary outcome, while objective response rate (ORR), overall survival (OS) and safety were secondary outcomes. Outcomes were compared by random/mixed-effects NMA using Bayesian (R software, Gemtc package) and frequentist (R software, netmeta package) approaches. Results: Twelve RCTs comparing 9 different treatment regimens with a total of 6805 patients were included for analysis. Hazard ratios (HR)/ odds ratio (OR)/ relative risk (RR) and 95% confidence intervals (CI) for PFS, ORR and grade> 3 adverse events (AE) of selected comparisons from the results of the NMA are shown in table. Conclusions: REG combined with CTX might be a potential alternative to conventional therapeutic options and could be considered as the best option for treating KRAS and BRAF mutated mCRC patients. Future RCTs are needed to confirm our results. [Table: see text]

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Addition of bevacizumab to first-line FOLFOX4 and overall survival in patients with metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.610 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 610-610 ◽

Cited By ~ 2

Author(s):

Mitsukuni Suenaga ◽

Satoshi Matsusaka ◽

Nobuyuki Mizunuma ◽

Eiji Shinozaki ◽

Mariko Ogura ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Median Overall Survival ◽

Progression Free Survival ◽

Line Treatment ◽

First Line ◽

Free Survival ◽

First Line Treatment

610 Background: In our previous report, addition of bevacizumab (BV) to the FOLFOX4 regimen appeared to significantly improve response rate, progression-free survival and overall survival in first-line treatment for patients with metastatic colorectal cancer (mCRC) (Suenaga M, et al. ASCO-GI 2011 [abstr 588]). Update results met median overall survival, and statistical analysis of survival was performed. Methods: An observational cohort study was carried out on all eligible patients scheduled to receive FOLFOX4 (n = 128) or FOLFOX4+BV (n = 85) between 2005 and 2007, 2007 and 2009, with a median follow-up time of 20.4 months vs. 30.2 months, respectively. Predefined efficacy endpoints were treatment characteristics, response rates, progression-free survival, and overall survival in the periods of time observed. Results: Median progression-free survival was 9.9 months (95% CI, 8.4-11.4) in the FOLFOX4- and 17 months (95% CI, 11.8-22.3) in the FOLFOX4+BV-treated patients (p=0.002). Median overall survival times were 20.5 months (95% CI, 16.9-24) and 38.8 months (95% CI, 32.9-44.8) in the two groups, respectively (p<0.001). In the ECOG PS 0 population, progression-free survival in the FOLFOX4 and FOLFOX4+BV groups was 11 months and 17 months with a hazard ratio of 0.63 (95% CI, 0.44-0.89) in favour of FOLFOX4+BV, similarly in OS with a hazard ratio of 0.53 (95% CI, 0.36-0.77). Subgroup population received 5-FU plus leucovorin (FL) as maintenance during oxaliplatin discontinuation due to adverse events had longer PFS or OS in both groups, though no significance. PFS were 14.7 and 21.6 months, and OS were 29 and 45.9 months, respectively. Secondary resection was performed more in FOLFOX4+BV (11.8%) than FOLFOX4 (3.9%) patients. Conclusions: These data indicate potential survival benefits from the addition of BV to the FOLFOX4 regimen as first-line treatment for mCRC. Maintenance using FL after discontinuation of oxaliplatin due to adverse events appeared to be an essential factor for better survival.

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Clinical utility of PEG-G-CSF for preventing severe neutropenia in metastatic colorectal cancer patients treated with FOLFOXIRI plus bevacizumab: A single centor retrospective study

10.21203/rs.2.14923/v1 ◽

2019 ◽

Author(s):

Kitagawa Yusuke ◽

Hiroki Osumi ◽

Eiji Shinozaki ◽

Yumiko Ota ◽

Izuma Nakayama ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Events ◽

Metastatic Colorectal Cancer ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Severe Neutropenia ◽

Free Survival ◽

The Common ◽

Grade 3 ◽

Colorectal Cancer Patients

Abstract Background: This study aimed to evaluate in clinical practice the efficacy and safety of polyethylene glycol conjugated granulocyte colony-stimulating factor (PEG-G-CSF) for preventing neutropenia in metastatic colorectal cancer (mCRC) patients that received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab (Bev). Methods: We retrospectively analyzed mCRC patients who received FOLFOXIRI plus Bev between December 2015 and December 2017. We evaluated the efficacy of PEG-G-CSF for treating neutropenia, the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors version 1.1, progression free survival (PFS), overall survival (OS), and adverse events of FOLFOXIRI plus Bev based on the Common Terminology Criteria for Adverse Events version 4.0. Results: A total of 26 patients (median age 53.5 years) were included. The ORR rate was 65.3%, the median PFS was 9.6 months (7.2–16.9), and the median OS was 24.2 months (13.6–NA). Grade 3 or 4 neutropenia occurred in 53.8% of the patients and febrile neutropenia occurred in 7.7%. PEG-G-CSF was given to 77.0% of the patients, including prophylactically (n = 9) and after the development of grade 3 or 4 neutropenia (n = 11). No patients experienced grade 3 or higher neutropenia after the administration of PEG-G-CSF. In seven of the nine patients who received PEG-G-CSF prophylactically (77.7%), no dose adjustment was required.Conclusions: PEG-G-CSF was useful in preventing severe neutropenia in mCRC patients treated with FOLFOXIRI plus Bev.

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