scholarly journals Cetuximab in treatment of metastatic colorectal cancer: background and clinical observation

2018 ◽  
pp. 32-41
Author(s):  
A. D. Darenskaya ◽  
N. V. Dobrova ◽  
B. M. Medvedeva
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Treatment Algorithms ◽  
Free Survival ◽  
Chemotherapy Drugs ◽  
Treatment Regimens ◽  
Improve Patient

Today, the researchers continue the search for the most optimal regimens of drug therapy for metastatic colorectal cancer (mCRC) which are supposed to increase progression-free survival (PFS) and overall survival (OS), improve patient quality of life. Due to significant progress in chemotherapy (CT) and surgical treatment of mCRC, and the multidisciplinary approach, the treatment algorithms have changed. The increase in life expectancy of patients is observed when all three of the most active chemotherapy drugs in this disease: oxaliplatin (Oxa), irinotecan (Iri), fluoropyrimidines are administered. The inclusion of the targeted drug cetuximab in modern mCRC treatment regimens led to a statistically significant increase in the objective response rate (ORR), median PFS and OS. The article presents the results of the most significant clinical studies of the eficacy of the antiEGFR drug cetuximab in combination with standard CT regimens for the first- and second-line treatment of mCRC, and describes a clinical case of the successful use of cetuximab in mCRC therapy.

Capecitabine, Bevacizumab, and Mitomycin in First-Line Treatment of Metastatic Colorectal Cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study

2010 ◽  
Vol 28 (19) ◽  
pp. 3191-3198 ◽  
Author(s):  
Niall C. Tebbutt ◽  
Kate Wilson ◽  
Val J. Gebski ◽  
Michelle M. Cummins ◽  
Diana Zannino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Free Survival ◽  
Treatment Regimens ◽  
The United Kingdom

Purpose To determine whether adding bevacizumab, with or without mitomycin, to capecitabine monotherapy improves progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) in an open-label, three-arm randomized trial. Patients and Methods Overall, 471 patients in Australia, New Zealand, and the United Kingdom with previously untreated, unresectable mCRC were randomly assigned to the following: capecitabine; capecitabine plus bevacizumab (CB); or capecitabine, bevacizumab, and mitomycin (CBM). We compared CB with capecitabine and CBM with capecitabine for progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, response rate (RR), and quality of life (QOL). Results Median PFS was 5.7 months for capecitabine, 8.5 months for CB, and 8.4 months for CBM (capecitabine v CB: hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.79; P < .001; C v CBM: HR, 0.59; 95% CI, 0.47 to 0.75; P < .001). After a median follow-up of 31 months, median OS was 18.9 months for capecitabine and was 16.4 months for CBM; these data were not significantly different. Toxicity rates were acceptable, and all treatment regimens well tolerated. Bevacizumab toxicities were similar to those in previous studies. Measures of overall QOL were similar in all groups. Conclusion Adding bevacizumab to capecitabine, with or without mitomycin, significantly improves PFS without major additional toxicity or impairment of QOL.

Phase II study of combination chemotherapy with biweekly cetuximab and irinotecan for wild-type KRAS metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 561-561
Author(s):  
S. Yuki ◽  
K. Shitara ◽  
M. Yoshida ◽  
D. Takahari ◽  
S. Utsunomiya ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Combination Chemotherapy ◽  
Response Rate ◽  
Standard Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Standard Regimen ◽  
Free Survival

561 Background: Weekly cetuximab and irinotecan is a standard regimen in heavily pretreated patients with metastatic colorectal cancer (MCRC). The aim of this study was to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pretreated MCRC harboring wild-type KRAS. Methods: Patients with wild- type KRAS MCRC that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included in this study. Cetuximab was administered at 500 mg/m2 biweekly with irinotecan. The primary endpoint was response rate. The secondary endpoints included adverse events, progression-free survival, and overall survival. The pharmacokinetics of cetuximab was also evaluated in five patients. Results: From May, 2009 to February, 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 assessable patients, ECOG PS was 0 in 12, 1 in 16, and 2 in two patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4), and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95%CI, 61.4-92.3). The median progression-free survival was 5.3 months (95%CI, 3.4-7.3). Grade 3 skin toxicity was observed in 3 patients (10%), and treatment related death due to pneumonia occurred in one patient. Conclusions: The efficacy data are similar to those of standard dose of cetuximab plus irinotecan. Combination chemotherapy with biweekly cetuximab and irinotecan is effective for pretreated metastatic wild-type KRAS MCRC. No significant financial relationships to disclose.

scholarly journals Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study

2019 ◽  
Vol 13 ◽  
pp. 117955491882544 ◽  
Author(s):  
Ali Aljubran ◽  
Mahmoud A Elshenawy ◽  
Magdy Kandil ◽  
Muhammed N Zahir ◽  
Ahmed Shaheen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Free Survival

Background: Regorafenib is a multi-kinase inhibitor approved for treatment of refractory advanced colorectal cancer. It was found in the clinical trials to have a modest benefit and significant toxicity. Our aim was to assess the outcome in our local clinic practice. Patients and methods: Records of patients with confirmed colorectal cancer treated with regorafenib were reviewed. Clinical, pathological, and molecular data were collected. Efficacy and factors of possible prognostic significance were analyzed. Results: A total of 78 patients with metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016 in 4 different institutions (median age: 50.5 years; male: 40 [51.3%]; KRAS mutant: 41 [52%]; right colonic primary: 18 [23%]). A total of 52 patients (66.7%) had Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1, whereas in 25 patients (32.1%) it was >1. In total, 58 patients (74%) had dose reduction. No patient achieved objective response, 15 patients (19%) achieved stable disease, and 56 patients (72%) had progressive disease. With a median follow-up of 6.5 months, the median progression-free survival was 2.8 months (95% confidence interval [CI], 2.5-3.3) and overall survival was 8.0 months (95% CI, 6.2-9.7). Only performance status of ⩽1 had a statistically significant impact on progression-free survival and overall survival in both univariate and multivariate analyses. Conclusions: Regorafenib in our clinical practice has equal efficacy to reported data from pivotal registration trials. Our data suggest that performance status is the most important prognostic factor in patients treated with regorafenib, suggesting a careful selection of patients.

A phase II trial of panitumumab with irinotecan and S-1 (IRIS) as second-line treatment in patients with wild-type KRAS metastatic colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 732-732
Author(s):  
Rai Shimoyama ◽  
Tetsuo Kimura ◽  
Toshi Takaoka ◽  
Kazuki Sakamoto ◽  
Shunji Kawamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Second Line ◽  
Wild Type ◽  
Free Survival ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy

732 Background: Panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in second-line chemotherapy increased objective response rate and prolonged progression-free survival (PFS) versus FOLFIRI alone in patients with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) (Peeters et al, J Clin Oncol 2010). This trial (UMIN000004659) evaluated tolerability and efficacy of combination therapy with irinotecan and S-1, an oral fluoropyrimidine (IRIS) plus panitumumab as second-line chemotherapy in patients with WT KRASmCRC. Methods: Main inclusion criteria were: patients with WT KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/m2) and irinotecan (100 mg/m2) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was completion rate of protocol therapy (CRT). The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Thirty-seven patients were enrolled in 9 centers. The overall CRT was 62.2% (23/37). Most frequent grade 3/4 toxicities were: skin rash (24%), diarrhea (16%), and appetite loss (11%). The overall RR was 32.4% (12/37). Of these, four patients underwent conversion surgery. Median PFS and OS were 9.5 months (95% CI: 3.5-15.4 months) and 20.1 months (95% CI: 16.7-23.2 months), respectively. Conclusions: IRIS plus panitumumab has acceptable toxicity profile and promising efficacy in patients with previously treated WT KRAS mCRC. This regimen can be an additional treatment option for second-line chemotherapy in WT KRAS mCRC. Clinical trial information: UMIN000004659.

Apatinib monotherapy for chemotherapy-refractory metastatic colorectal cancer: A multicenter, single-arm, prospective study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3527-3527 ◽  
Author(s):  
Fen Wang ◽  
Shubin Wang ◽  
Xia Yuan ◽  
Jun Jia ◽  
Xiaoxia Bi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prospective Study ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Free Survival

3527 Background: Apatinib is an oral highly-selective tyrosine kinase inhibitor (TKI) that blocks vascular endothelial growth factor receptor 2 (VEGFR-2). This exploratory study evaluated the efficacy and safety of apatinib monotherapy in patients with chemotherapy-refractory metastatic colorectal cancer. Methods: In this multicenter, single-arm, prospective study, 48 patients with metastatic colorectal cancer who had failed at least two lines standard chemotherapies including fluorouracil, oxaliplatin and irinotecan were recruited from 14 centers in Guangdong, China. Apatinib at a 500mg dose was administered daily continuously. Each cycle was 4 weeks (28 days). The primary endpoint was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. Results: A total of 48 patients was enrolled in the study from September 3, 2015 to June9, 2017. Four patients achieved a partial response, and 22 achieved stable disease, representing a response rate of 8.3% and a disease control rate of 60.4%. Median follow-up time was 10.3 months. Median progression-free survival (PFS) and overall survival (OS) of evaluable patients (n=41) were 4.7 months (95% confidence interval [CI] 3.7-5.9) and 9.7 months (95% CI 5.9-13.6). The most common grade 3 or 4 adverse events (AE) were hypertension (12.5%), hand-foot syndrome (10.4%), thrombocytopenia (10.4%), proteinuria (8.3%) and mucositis oral (6.3%). Conclusions: Apatinib monotherapy shows promising efficacy and manageable toxicities in patients with chemotherapy-refractory metastatic colorectal cancer. Further phase 3 trial is warranted. Clinical trial information: ChiCTR1900020503.

scholarly journals FOLFOXIRI versus FOLFOX or FOLFIRI with targeted therapy in patients with mutant BRAF metastatic colorectal cancer: A systematic review and meta-analysis

2020 ◽  
pp. 125-132
Author(s):  
M. Yu. Fedyanin ◽  
E. M. Polyanskaya ◽  
H. H.-M. Elsnukaeva ◽  
A. A. Tryakin ◽  
I. A. Pokataev ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Metastatic Colorectal Cancer ◽  
Subgroup Analysis ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Systemic Review ◽  
Free Survival

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I2 = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I2 = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I2 = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1st line for pts with mBRAF mCRC.

scholarly journals EFFECTIVENESS OF MAINTENANCE THERAPY AFTER THE END OF THE FIRST LINE OF TREATMENT FOR PATIENTS WITH METASTATIC COLORECTAL CANCER – THE RESULTS OF A POPULATION-BASED STUDY

2018 ◽  
Vol 8 (3) ◽  
pp. 57-67
Author(s):  
M. Yu. Fedyanin ◽  
Sh. A. Aliyeva ◽  
L. Y. Vladimirova ◽  
A. N. Ivanov ◽  
A. A. Katkov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Observation Group ◽  
First Line ◽  
Free Survival ◽  
Maintenance Group

Aim.To evaluate the effectiveness of different regimens of maintenance chemotherapy after the first line of treatment for patients with metastatic colorectal cancer.Materials and methods.We performed retrospective analyses of the data from 432 patients from 17 clinics in 14 regions of the Russian Federation who started systemic therapy for metastatic cancer in 2013. The main inclusion criterion was objective response or stabilization after the first 16 weeks of first-line therapy. Four groups of patients were compared, depending on the nature of maintenance therapy: those receiving fluoropyrimidines, a combination of fluoropyrimidines with bevacizumab, monotherapy of bevacizumab and monotherapy of anti-EGFR antibodies. The main criteria for assesment of the effectiveness of treatment were progression-free survival and overall survival. The statistical analysis was performed with the SPSS 20.0 sof tware package.Results.Maintenance therapy after completion of the first 16 weeks of the 1st line of chemotherapy was administered in 126 patients, most of them were treated with fluoropyrimidines (53.1 %). The median overall survival in the maintenance group was 27 versus 21 months in the observation group, p=0.01, HR=0.78 (95 % CI 0.6–1.02) Median progression-free survival in the maintenance group was 11 vs 7 months in the observation group (p<0.001, HR=0.6, 95 % CI 0.5–0.8). The worst results of progression-free survival were observed in the group with monotherapy of bevacizumab – median was 10 months versus 12 months in the fluoropyrimidine monotherapy group, 10 months for the combination of fluoropyrimidine with bevacizumab and 14 months for monotherapy of the anti-EGFR (p=0,9, HR=1.0, 95 % CI 0.9–1.2).Conclusions.There were no statistical differences in survival with different regimens of maintenance therapy. Monotherapy of bevacizumab in maintenance treatment was associated with the worst sur vival rates.

ICE CREAM: Irinotecan cetuximab evaluation and the cetuximab response evaluation among patients with G13D mutation.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS3649-TPS3649 ◽  
Author(s):  
Eva Segelov ◽  
Kate Wilson ◽  
Val Gebski ◽  
Paul Michael Waring ◽  
Josep Tabernero ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Similar Response ◽  
Kras Mutations ◽  
Free Survival ◽  
Synthase Inhibitor ◽  
Clinical Trial Information

TPS3649 Background: Patients with metastatic colorectal cancer (mCRC) whose disease has progressed despite oxaliplatin and irinotecan containing regimens may benefit from the use of EGFR-inhibiting monoclonal antibodies if the tumor contains no mutations in the KRASgene (i.e. WT). However, it is unknown whether antibodies used in this setting, such as cetuximab, are more efficacious alone or in combination with irinotecan, as suggested by the BOND study which did not select for KRASstatus. This international trial will also evaluate prospectively the activity of cetuximab in the subgroup of patients with mCRC with a specific KRASmutation in codon G13D. In selected retrospective analyses, tumors bearing this mutation appear to derive similar response from cetuximab as WT. Trials involving small molecular subsets (in this case approx. 5% of patients with mCRC, or 18% of patients with KRAS mutations) will provide framework for future collaborations. Methods: This randomised phase II study of cetuximab +/- irinotecan will recruit patients with metastatic colorectal cancer (mCRC) with either KRAS WT (n=50) or G13D mutation (n=50) over 2 years from sites in Australia (12), and three international sites (G13D mutations only): Spain (1), England (1), and Italy (1). The trial will prospectively select the KRAS WT arm for the “quadruple WT" genotype (no mutations also in BRAF, NRAS, PIK3CA exon20). Primary objective is 6 month progression free survival. Secondary objectives are response rate, overall survival, quality of life, and translational research including markers that may predict response such as amphiregulin and epiregulin determined by immunohistochemistry. Eligibility: Patients with histologically confirmed CRC with either “quadruple WT" genotype or KRAS G13D mutation; unresectable metastatic disease; measurable or evaluable disease; ECOG 0-2; life expectancy at least 12 weeks, and disease progression, or intolerance of thymidylate synthase inhibitor and irinotecan and oxaliplatin containing regimens. Status: Opened to accrual November 2012, at 31 Jan 2013 3/100 patients have been enrolled, all with G13D mutations. Clinical trial information: ACTRN12612000901808.

A retrospective study of raltitrexed combined with S-1 as salvage treatment for patients with metastatic colorectal cancer after failure of standard chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15066-e15066 ◽  
Author(s):  
Weijian Guo ◽  
Zhenhua Wu ◽  
Mingzhu Huang ◽  
Xiaowei Zhang
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cross Resistance ◽  
Line Treatment ◽  
Free Survival ◽  
Daily Dose ◽  
Third Line ◽  
Grade 3

e15066 Background: The FOLFOX regimen consisting of fluorouracil (5-FU) and oxaliplatin, and the FOLFIRI regimen consisting of 5-FU and irinotecan serve as either first- or second-line treatment for metastatic colorectal cancer (mCRC), and there is no third-line chemotherapy regimen after failure of 5-FU, oxaliplatin, and irinotecan. Studies have shown that raltitrexed or S-1 has no complete cross-resistance with 5-FU and may be used for mCRC after failure of 5-FU. In the present study, we retrospectively analyzed the efficacy and safety of raltitrexed combined with S-1 in the treatment of mCRC after failure of conventional chemotherapy. Methods: Eighteen patients with mCRC treated with raltitrexed combined with S-1 after failure of fluorouracil, oxaliplatin and irinotecan between February 2014 and August 2016 were included in this study. Raltitrexed (3 mg/m2) intravenous infusion was given on the first day, and the administration of S-1 (daily dose according to body surface area (BSA): 100 mg/day when BSA ≥1.25 m2 to < 1.5 m2; 120 mg/day when BSA≥1.5 m2) continued for 2 weeks, and stopped for one week. The regimen was repeated every 3 weeks. Tumor response was evaluated according to RECIST 1.1 criteria. Toxicity was graded according to NCI-CTC 4.0 version. Results: Among 18 patients, 2 had PR, 8 had SD, and 8 had PD. The ORR (objective response rate) was 11.1%, and the DCR (disease control rate) was 55.6%. The median PFS (progression free survival) and OS (overall survival) were 2.5 months and 7.0 months respectively. Adverse reactions included fatigue, abnormal liver enzymes, neutropenia, stomatitis, pyrexia, arrhythmia, hypertension, diarrhea, nausea and most of these were grade 1-2. Only one patient had grade 3 neutropenia and grade 3 diarrhea. Conclusions: The combination of raltitrexed and S-1, both of which targeting TS, preliminarily showed promising effects for metastatic colorectal cancer after failure of standard chemotherapyand may be used as third-line treatment regimen.

Efficacy and safety of regorafenib compared to TAS-102 for metastatic colorectal cancer: A systematic review and network meta-analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 735-735
Author(s):  
Ana Beatriz Kinupe Abrahao ◽  
Yoo-Joung Ko ◽  
Kelvin K. Chan ◽  
Scott R. Berry
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Meta Analyses

735 Background: Recent studies have shown regorafenib and TAS-102 (TAS) to be superior to placebo (P) in refractory metastatic colorectal cancer (mCRC). However, no studies have directly compared both drugs. Giving the lack of therapeutic options for these patients,, a systematic review to compare the efficacy and safety of regorafenib compared with TAS was performed, using indirect comparison methods. Methods: A systematic review using PubMed, Medline, Embase, Scopus and Cochrane database to identify published and unpublished studies up to November 2015 for randomized controlled trials (RCTs) for patients with metastatic colorectal cancer, involving regorafenib or TAS was performed. Data including overall survival (OS), progression-free survival (PFS) and toxicity were extracted. Pairwise direct meta-analyses (regorafenib versus placebo and TAS versus placebo) and indirect comparison (regorafenib versus TAS) using network meta-analyses methods (R package “netmeta”) to preserve randomization were performed using random effects. Results: 914 citations were initially identified among which 3 RCTs fulfilled eligibility criteria (CORRECT, CONCUR and RECOURSE trials) involving 1.764 patients (regorafenib: 641, TAS: 534, Placebo: 589). Subgroups of patients (1.659) who had not received prior regorafenib or TAS-102 were used to performed meta-analyses for efficacy. In indirect comparison, there were no statically differences observed between regorafenib and TAS-102 in overall survival (HR 0.96 95% CI 0.56-1.55 p = 0.082) and progression-free survival (HR HR 0.85 95% CI 0.40-1.80 p = 0.0182). In addition, there were no differences in objective response rate and disease control between both drugs. However, regorafenib has statistically more all grade toxicity (risk difference (RD) 0.31 CI 0.25-0.38 p = 0.001) and toxicity grade 3-5 (RD 0.22 CI 0.13-0.31 p < 0.001) compared to TAS. Conclusions: In this indirect comparison, regorafenib and TAS appeared to have similar efficacy. However, regorafenib has more toxicity compared to TAS. Post-approval real world data focusing on the comparative toxicity of regorafenib and TAS is warranted.

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