Dataset Information

Association Between Regorafenib Dose and Efficacy Against Metastatic Colorectal Cancer in a Real-World Setting.

ABSTRACT: The association between regorafenib dosage in the treatment of metastatic colorectal cancer (mCRC) and efficacy is currently not well established. It was previously reported that the regorafenib dose as prescribed is associated with efficacy, but doses in actual clinical settings have not been analyzed. We retrospectively analyzed patients with mCRC who had received regorafenib as third-line or later chemotherapy between May 2013 and June 2018. Patients who were not treated in the Pharmaceutical Outpatient Clinic for compliance assessment were excluded. Overall survival was calculated using the Kaplan-Meier method. Prognostic factors, including baseline demographics and adverse events, were evaluated using Cox proportional hazard models. A total of 176 patients were enrolled. By multivariate analysis, total dose until the second cycle < 3180 mg (HR = 1.71, 95% CI, 1.20-2.44, P = .003) was one of independent negative predictors of overall survival. Median survival times of the lower-dose group (< 3180 mg) and higher-dose group (≥ 3180 mg) were 5.8 and 7.6 months, respectively (P = .045). The cumulative dose of regorafenib until the second cycle in patients with mCRC was associated with survival. It is important to individualize regorafenib dose in mCRC patients.

SUBMITTER: Hatori M

PROVIDER: S-EPMC8524711 | biostudies-literature | 2021 Oct-Dec

REPOSITORIES: biostudies-literature

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Association Between Regorafenib Dose and Efficacy Against Metastatic Colorectal Cancer in a Real-World Setting.

Hatori Masahiro M Kawakami Kazuyoshi K Wakatsuki Takeru T Shinozaki Eiji E Kobayashi Kazuo K Aoyama Takeshi T Nakano Yasuhiro Y Suzuki Kenichi K Yamaguchi Kensei K Hama Toshihiro T

Dose-response : a publication of International Hormesis Society 20211012 4

The association between regorafenib dosage in the treatment of metastatic colorectal cancer (mCRC) and efficacy is currently not well established. It was previously reported that the regorafenib dose as prescribed is associated with efficacy, but doses in actual clinical settings have not been analyzed. We retrospectively analyzed patients with mCRC who had received regorafenib as third-line or later chemotherapy between May 2013 and June 2018. Patients who were not treated in the Pharmaceutical ...[more]

PMID: 34675759

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Project description:BackgroundFruquintinib and regorafenib have been approved for the third-line therapy of metastatic colorectal cancer (mCRC) in China. However, at present, there is a lack of head-to-head clinical trials on the comparison of efficacy and safety between the two drugs.Materials and methodsThe data of patients with mCRC who were treated with fruquintinib or regorafenib after the standard chemotherapy in Zhejiang Provincial People's Hospital from October 2018 to November 2021 were collected and analyzed. The primary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. The secondary endpoints were the appropriate sequence, objective remission rate (ORR) and disease control rate (DCR) of fruquintinib and regorafenib.ResultsA total of 105 patients were enrolled in this study. The ORR of fruquintinib group (n=55) and regorafenib group (n=50) were 6.1% and 2.0%; the DCR were 65.3% and 54.2%, respectively. There was no significant difference in median OS (mOS) and PFS (mPFS) between the two groups (mOS:14.2 vs12.0 months, p=0.057; mPFS:4.4 vs 3.5 months, p=0.150). Combined immunotherapy showed a synergistic effect. The mPFS and mOS of fruquintinib combined with anti-PD-1 therapy were longer than those of fruquintinib monotherapy (mPFS:5.9 vs 3.0 months, p=0.009; mOS:17.5 vs 11.3 months, p=0.008). The mOS of patients treated with regorafenib combined with anti-PD-1 therapy was 14.8 months higher than that of regorafenib monotherapy (p=0.045). When combined with anti-PD-1 therapy, the mPFS and mOS of fruquintinib was significantly longer than regorafenib (mPFS:5.9 vs 3.8 months, p=0.018; mOS:17.5 vs 14.8 months, p=0.044). In the treatment sequence, the OS of patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence (15.0 vs 8.3 months, p=0.019). The adverse reactions were generally similar, but the incidence of hand-foot syndrome of regorafenib was higher than that of fruquintinib, while fruquintinib was more prone to grade 3 hypertension.ConclusionFruquintinib monotherapy showed better disease control rate and objective remission rate in the post-line therapy of metastasis colorectal cancer. Notably, the combination of PD-1 immunotherapy brought the additional effect, especially in the fruquintinib combined with anti-PD-1 therapy. Patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence. The toxicity of fruquintinib and regorafenib are similar.

Project description:BackgroundRaltitrexed plus S-1 (RS) and regorafenib both showed considerable efficacy for metastatic colorectal cancer (mCRC) patients. This study aims to compare the effectiveness and safety of two different regimens in patients with refractory mCRC.MethodsThis retrospective cohort study included mCRC patients who were treated with RS or regorafenib from February 2017 to June 2021. A propensity score matching (PSM) analysis was conducted to balance the baseline characteristics of all patients. Progression-free survival (PFS), overall survival (OS), tumor response, and safety of two regimens were evaluated.ResultsA total of 187 patients were included in our study, with 107 patients in the RS group and 80 patients in the regorafenib group. After PSM, 78 pairs were recognized. Patients treated with RS had a semblable PFS compared to those treated with regorafenib before PSM (4.8 months vs 5.5 months, p = 0.400) and after PSM (4.7 months vs 5.4 months, p = 0.430). Patients in the RS group were associated with a longer OS than those in the regorafenib group (13.4 months vs 10.1 months, p = 0.010). A similar trend of OS was also obtained in the matched cohort (13.3 months vs 10.0 months, p = 0.024). Both objective response rate (12.8% vs 5.1%, p = 0.093) and disease control rate (53.8% vs 46.2%, p = 0.337) in the RS cohort were higher than those in the regorafenib group, without significant differences. Adverse events (AEs) of each group were well tolerated.ConclusionPatients treated with RS demonstrated a longer OS than those treated with regorafenib and had manageable AEs, which could be recognized as a primary choice for refractory mCRC.Plain language summaryEfficacy and Safety of Raltitrexed plus S-1 Versus Regorafenib in Patients with Refractory Metastatic Colorectal Cancer: A Real-world Propensity Score Matching StudyBoth raltitrexed plus S-1 (RS) and regorafenib showed considerable efficacy for metastatic colorectal cancer (mCRC) patients. No study has compared the two regimens yet. Therefore, we compare the efficacy and safety between RS and regorafenib to provide an optimal treatment option. We retrospectively included patients with mCRC who failed at least two standard treatments. All enrolled patients received RS or regorafenib treatments. We conducted a propensity score matching to eliminate differences in the enrolled patients. After the analysis, we found no significant differences in progression-free survival in patients between the two groups. However, patients treated with RS had a longer OS than those treated with regorafenib, whether before matching (13.4 months vs 10.1 months, p = 0.010) or after matching (13.3 months vs 10.0 months, p = 0.024). In addition, the adverse effects caused by cancer-related therapy were tolerable for the patient. Certainly, this is a non-randomized retrospective study with a small sample size, so we conducted a propensity score matching to minimize potential bias. Importantly, this is the first research comparing the two treatments, and we believe that the results of this article could present a primary choice for clinical doctors dealing with patients with standard treatments that failed mCRC.

Project description:BackgroundThe randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines.MethodsPatients with CRC in the Optum's de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group.Results703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1).ConclusionsFollowing inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.

Project description:Regorafenib is an orally administered multikinase inhibitor that has been approved for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Even though regorafenib significantly improved survival in two international phase 3 trials (CORRECT and CONCUR), a high rate of treatment-related toxic effects and dose modifications were observed with a modest benefit. The aim of this study was to provide information concerning the efficacy, safety, and cost of regorafenib in patients with mCRC in clinical practice.We retrospectively reviewed patients treated with regorafenib monotherapy for unresectable mCRC in five Franche-Comté cancer hospitals (France). The primary end point was overall survival. Secondary end points were safety and descriptive cost analyses of patients treated with regorafenib in clinical practice. Another aim of this study was to assess the impact of regorafenib prescription on the risk of hospitalization in real-life practice.From January 2014 to August 2014, 29 consecutive patients were enrolled. Patients were heavily pretreated and were refractory to standard chemotherapies. The primary tumor sites were the colon and the rectum for 55% and 45% of patients, respectively. Fifteen patients (51%) harbored an RAS mutation. Eastern Cooperative Oncology Group - Performance Status (PS) was 0-1 for 86% of patients and 2 for 14% of patients. Nineteen patients (66%) initially received reduced doses of 120 or 80 mg/day. The median duration of treatment was 2.5 months (range, 0.13-11.4 months). Treatment-related adverse events occurred in 86% of patients. The most frequent adverse events of any grade were fatigue (35%), diarrhea (20%), and hand-foot skin reaction (20%). Grade 3 or 4 treatment-related adverse events occurred in 10 patients (35%). Three patients (10%) were admitted to hospital due to drug-related severe adverse events. The mean cost of patient management with regorafenib for the duration of treatment was 9908 ± 8191€, and median cost was 7917€ (Interquartile range (IQR) 4469-13,042). The median overall survival was six months (95% confidence interval, five to eight months).The safety and efficacy of regorafenib in heavily pretreated mCRC patients was comparable, in our study, to prospective and retrospective trials. Toxic effects were mostly manageable in an outpatient setting. Regorafenib itself represented the most important (93%) part of supported costs. Even though most side effects were manageable in an outpatient setting, severe adverse events occurred from hospitalization in 10% of patients. These data should be confirmed in a larger real-life-based cohort. Identification of predictive biomarkers is needed for mCRC patient selection for regorafenib treatment.

Dataset Information

Association Between Regorafenib Dose and Efficacy Against Metastatic Colorectal Cancer in a Real-World Setting.

Publications

Association Between Regorafenib Dose and Efficacy Against Metastatic Colorectal Cancer in a Real-World Setting.

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