scholarly journals Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice

2016 ◽  
Vol 10 ◽  
pp. CMO.S38335 ◽  
Author(s):  
Fabien Calcagno ◽  
Sabrina Lenoble ◽  
Zaher Lakkis ◽  
Thierry Nguyen ◽  
Samuel Limat ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Practice ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Real Life ◽  
Outpatient Setting ◽  
Toxic Effects ◽  
Duration Of Treatment ◽  
Heavily Pretreated

Background 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. Material and Methods 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. Results 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). Conclusions 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.

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

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 610-610 ◽  
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.

Safety and efficacy of trifluridine/tipiracil (FTD/TPI) plus bevacizumab in clinical practice for patients with chemorefractory metastatic colorectal cancer: A retrospective comparative study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 112-112
Author(s):  
Yoshinori Kagawa ◽  
Yohei Nose ◽  
Taishi Hata ◽  
Kenji Kawai ◽  
Takuya Sakamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Combination Regimen ◽  
Safety And Efficacy ◽  
Significant Difference ◽  
Retrospective Comparative Study ◽  
Practice Methods

112 Background: Trifluridine/tipiracil (FTD/TPI) significantly improves overall survival (OS) in patients with chemorefractory metastatic colorectal cancer (mCRC). The phase I/II C-TASKFORCE study of FTD/TPI + bevacizumab (Bev) for patients with mCRC who are refractory to standard chemotherapy demonstrated promising efficacy results. FTD/TPI + Bev were linked to significant and clinically relevant improvements in progression-free survival (PFS) and OS compared with FTD/TPI monotherapy and a favorable safety profile in a Danish randomized trial. This retrospective study investigated the safety and efficacy of FTD/TPI alone or in combination with Bev for patients with refractory mCRC in clinical practice. Methods: We reviewed the outcomes of patients with chemorefractory mCRC who received FTD/TPI alone (monotherapy; 35 mg/m2, twice daily on days 1–5 and 8–12 in a 28-day cycle) or FTD/TPI + Bev (combination; 5 mg/kg, days 1 and 15) in our institution since 2014. We compared the safety and efficacy of the monotherapy and combination regimens. Adverse events were evaluated using Common Terminology Criteria for Adverse Eventsv4.0. Median PFS and OS were analyzed using the Kaplan–Meier method. Results: In total, 56 patients received chemotherapy containing FTD/TPI. Twenty-four patients were treated with monotherapy, and 32 patients received the combination regimen. The median PFS was 1.8 months in the monotherapy arm, versus 4.7 months in the combination arm (hazard ratio [HR] = 0.28; 95% confidence interval [CI] = 0.15–0.51; P < 0.0001). The median OS was 6.3 months for the monotherapy arm, versus 11.7 months for the combination arm (HR = 0.25; 95% CI = 0.13–0.48; P < 0.0001). There was no significant difference in the rates of adverse events between the groups excluding neutropenia. Neutropenia (Grade 3 or worse) developed in five patients (20.8%) in the monotherapy arm and 17 patients (53.1%) in the combination arm ( P = 0.030). There were no treatment-related deaths. Conclusions: In patients with chemorefractory mCRC, FTD/TPI + Bev significantly improved PFS and OS versus FTD/TPI monotherapy.

scholarly journals Factors associated with Trifluridine/Tipiracil (TAS-102) effectiveness in patients with refractory metastatic colorectal cancer: real-life data from the Czech Republic.

2019 ◽  
Author(s):  
Peter Grell ◽  
Josef Dvorak ◽  
Michal Vocka ◽  
Stanislav John ◽  
Helena Pitauerova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Czech Republic ◽  
Clinical Practice ◽  
High Risk ◽  
Metastatic Colorectal Cancer ◽  
Scoring System ◽  
Risk Group ◽  
Real Life ◽  
The Czech Republic ◽  
Factors Associated

Abstract Background: Trifluridine/tipiracil (TAS-102) is effective in refractory metastatic colorectal cancer (mCRC). Currently, no predictive biomarkers are established and used in clinical practice. Methods: We analyzed data of 160 patients treated with TAS-102 in real clinical practice in the Czech Republic. Different factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated. Results: Median PFS was 3.3 months, and median OS 10.2 months. Factors significantly associated with PFS and/or OS were: ECOG performance status (PS), time from diagnosis of mCRC > 24 months, initiation of treatment > 3 months from last fluoropyrimidine, number of metastatic sites, baseline CRP level, WBC count, neutrophils count, monocytes count, neutrophil to lymphocyte ratio, development of neutropenia, thrombocytopenia, diarrhea, required dose reduction and cycle delay. We developed a scoring system TAScore from factors available at the beginning of treatment. One point each was assigned to the following factors (PS, diagnosis of mCRC > 24 months, initiation of TAS-102 > 3 months from fluoropyrimidine, baseline CRP, WBC, monocytes count < 0.5 × 10 9 /L) and patients were divided into 3 groups: high risk group (0 to 1 point), intermediate (2 to 3), favorable with 4 or more points. OS according to risk group was: 5.7 months for high risk, 8.7 for intermediate, 12.8 for favorable (P < 0.001). TAScore was also associated with PFS (P < 0.001). Conclusions : TAS-102 is effective in patients with refractory mCRC. We propose simple scoring system TAScore to help with precise patient selection at the beginning of TAS-102 treatment.

scholarly journals Effect of starting dose of regorafenib on overall survival of patients with metastatic colorectal cancer: a systematic review and meta-analysis

2019 ◽  
Vol 21 (3) ◽  
pp. 10-15
Author(s):  
Mikhail Yu Fedyanin ◽  
Elizaveta M Polyanskaya ◽  
Alexey A Tryakin ◽  
Ilia A Pokataev ◽  
Sergei A Tjulandin
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Clinical Practice ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Research Data ◽  
Routine Clinical Practice ◽  
Starting Dose ◽  
Review Manager

Aim. To conduct a systematic review and meta-analysis of studies on the effect of starting dose of regorafenib on overall survival (OS) of patients with chemorefractory metastatic colorectal cancer. Materials and methods. We searched for research data in the PubMed. The analysis included all publications till 08.20.2019 which compared OS depending on the starting dose of regorafenib (160 mg or less) in the 1st course of therapy. Meta-analysis was conducted using Review Manager Ver. 5.3. Results. Two studies demonstrated decreased OS at starting dose of less than 160 mg (A. Adenis et al., 2016: risk ratio - RR 1.26, 95% confidence interval - CI 1.01-1.56; A. Aljubran et al., 2019: RR 2.25, 95% CI 0.93-5.43). Two studies showed an improvement in OS with a starting dose of less than 160 mg in the 1st course (T. Bekaii-Saab et al., 2018: RR 0.72, 95% CI 0.47-1,11; J. Gotfrit et al., 2017: RR 0.46, 95% CI 0.17-1.22). In two other studies, there was no effect of a starting dose of regorafenib on OS (K. Yamaguchi et al., 2019: RR 0.95, 95% CI 0.82-1.1; G. Argiles et al., 2019: RR 0,86, 95% CI 0.65-1.13). The meta-analysis did not reveal the effect of starting dose of the drug on OS: RR 0.97, 95% CI 0.78-1.21; p=0.79; I2=64. Conclusions. Reducing the starting dose of regorafenib in the 1st course does not decrease OS and can be recommended for routine clinical practice.

Cetuximab in first-line treatment of metastatic colorectal cancer in a real-life setting: Preliminary results of the EREBUS cohort.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 621-621
Author(s):  
Denis Smith ◽  
Magali Rouyer ◽  
Emmanuel Mitry ◽  
Alain Monnereau ◽  
Antonio Sa Cunha ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Tumor Resection ◽  
Real Life ◽  
Line Treatment ◽  
Duration Of Treatment ◽  
Preliminary Results ◽  
Administration Regimen ◽  
Real Life Setting ◽  
Metastatic Sites

621 Background: Cetuximab (CTX) has demonstrated to improve survival outcomes in metastatic colorectal cancer (mCRC), but little data for real-life use is available. Methods: EREBUS is a French multicentre (n=92) hospital-based cohort. Patients initiating CTX in 2009 and 2010 were identified retrospectively from registries of nominative drug dispensations. Those with wild-type KRAS gene receiving 1st-line treatment for mCRC were followed-up for 12 months. Data were collected from patient medical records and response based on physician assessments (CT-Scan). Presented here are preliminary results of the EREBUS cohort about administration regimen and according response rates for patients included in 2009. Results: Of the 190 patients included in the cohort, data has been collected for 160 (84.2%): median age at baseline 65.5 years, 70.6% male. Regarding cancer characteristics, 79.4% of patients had a colon cancer and 53.8% a primary tumor resection. Metastatic sites were liver in 73.1% of patients, peritoneum in 29.4%, lymph nodes in 26.3%, and lung in 25.6%. For patients for which the ECOG status was available (54.4%): 79.3% have an ECOG score between 0 and 1, 20.7% ≥2. Half the patients (48.8%) had only one metastatic site. CTX was given every three weeks to 2 patients (1.3%), every two weeks to 113 of patients (70.6%), and weekly to 45 (28.1%). For those receiving CTX every two weeks: 64.9% had irinotecan-based regimens (vs. 45.5% of those receiving CTX weekly, p=0.03), 31.5% had oxaliplatin-based regimens (vs. 47.7%, p=0.06), median duration of CTX use was 3.8 months (vs. 5.3 months, p=0.69) and that of 1st-line therapy 6.3 months (vs. 7.5 months, p=0.97), 69.0% discontinued 1st-line treatment (vs. 82.2%, p=0.09) – mainly for progression (71.8 vs. 75.7%, p=0.66) or toxicity (20.5 vs. 10.8%, p=0.20). Overall response evaluated for 100 patients receiving CTX every two weeks out of 113 was 46.0% (vs. 52.6%, p=0.49, evaluated for 38 receiving CTX weekly). Conclusions: CTX administration every two weeks was the most frequent regimen. In this preliminary analysis, patients receiving weekly or every two weeks regimens had similar duration of treatment and response rate.

Safety for trifluridine/tipiracil (TAS-102) with bevacizumab combination in patients with refractory metastatic colorectal cancer in real-world clinical practice: The single-institutional experience.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 865-865
Author(s):  
Kayo Yasuda ◽  
Daisuke Kotani ◽  
Yasutoshi Kuboki ◽  
Shota Fukuoka ◽  
Hideaki Bando ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Practice ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Task Force ◽  
Phase 1 ◽  
Performance Status ◽  
Perianal Abscess ◽  
Ecog Performance Status

865 Background: Trifluridine/tipiracil (TAS-102) is an oral combination therapy approved for the treatment of patients with metastatic colorectal cancer (mCRC). Phase 1/2 C-TASK FORCE study of TAS-102 plus bevacizumab for patients with refractory mCRC demonstrated a promising efficacy results with mild toxicity profile (Kuboki Y, et al. Lancet Oncology, 2017). The retrospective single-institutional study is aiming to investigate safety of TAS-102 plus bevacizumab for patients with refractory mCRC in real-world clinical practice. Methods: MCRC patients who were refractory or intolerant to a fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (if wild-type RAS) and consecutively received TAS-102 plus bevacizumab between January 2016 and June 2017, were analyzed. Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Results: A total of 33 patients were identified for safety analysis. Patient characteristics were as follows; male/female, 19/14; median age, 59.0 (range 38-81); ECOG Performance Status of 0/1, 21/12; and All wild/ RAS mutant/ BRAF mutant/ unknown, 16/15/1/1. Six patients had received prior regorafenib. The relative dose intensities of TAS-102 and bevacizumab were 87% and 79%, respectively. Grade 3 or higher hematological and non-hematological AEs were follows; leucopenia, 33%; neutropenia, 42%; anemia, 9%; and proteinuria, 12%. There were no febrile neutropenia or treatment-related death. G-CSF was given in 8 patients (24%), while intravenous antibiotics was in one patient. There were four patients with emergency admission, and out of these, the two patients had intestinal perforation, and perianal abscess, which were regarded as treatment-associated; ultimately these AEs were fully recovered. Conclusions: Our findings suggested safety for TAS-102 plus bevacizumab combination in real-world clinical practice is consistent with those in clinical trial setting.

Bevacizumab combined with first-line chemotherapy in elderly patients (≥75 years old) with metastatic colorectal cancer: Final results of the noninterventional CASSIOPEE study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3547-3547
Author(s):  
Eric Francois ◽  
Denis Michel Smith ◽  
Sophie Gourgou ◽  
Sophie Gandon ◽  
Florence Rollot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Real Life ◽  
Progression Free Survival ◽  
Daily Practice ◽  
Similar Treatment ◽  
Free Survival ◽  
Metastatic Sites ◽  
Efficacy Population

3547 Background: Approximately half of the patients (pts) with metastatic colorectal cancer (mCRC) are elderly (≥65 years). Although few elderly pts are included in clinical studies, results in mCRC have shown similar treatment benefits in terms of progression-free survival and overall survival in young and elderly pts. This study was conducted in pts ≥75 years-old with mCRC treated in real life 1st line bevacizumab + chemotherapy in order to improve the knowledge on this population and to contribute in optimizing treatment strategy. Methods: CASSIOPEE is a prospective, multicenter, non-interventional study evaluating 1st line combination of bev + chemotherapy over 24 months in pts aged ≥75 years with mCRC. The primary endpoint was to describe progression-free survival (PFS). Secondary endpoints included the description of pts characteristics, overall survival, bev and chemotherapy regimen, safety and autonomy criteria (Lawton Instrumental Activities of Daily Living Scale; Balducci score). Results: A total of 402 pts were included between March 2012 and July 2016. In the efficacy population (n = 358), 52% were men, mean age 81 (±4); 54% were≥ 80 years old and 19% were ECOG ≥2; 80% had primary tumor located in the colon; main metastatic sites: liver (66%) and lung (30%). Bev was mainly combined with Folfox (36%) and Folfiri (29%). Median PFS was 9.1 months [8.3;10.2] in the efficacy population and 9.3 months for pts aged < 80, 9.5 months for pts aged ≥ 80 or ≤ 85 and 8.3 months for pts aged > 85. The PFS rate at 24 months was 11.8%. Median OS was 19.0 months [16.5;21.5] in the efficacy population and 20.6 months for pts aged < 80, 17.8 months for pts aged ≥ 80 or ≤ 85 and 13.0 months for pts aged > 85. The OS rate at 24 months was 42.0%. Autonomy and ECOG status remained stable from baseline to 24 months. In the safety population (n = 383), grade ≥ 3 adverse events occurred in 40% pts including 10% pts with bev related AEs. Overall, 4% pts died of an AE and 0.5% were bev related. Conclusions: These results suggest that mCRC patients aged ≥75 years-old, can benefit from 1st line bev plus chemotherapy in daily practice in this population. The safety profile is acceptable. Clinical trial information: NCT01555762.

scholarly journals TAS-102 in metastatic colorectal cancer (mCRC): efficacy, tolerability, and quality of life in heavily pretreated elderly patients: a real-life study

2020 ◽  
Vol 9 ◽  
pp. 1-8
Author(s):  
Giuseppe Cicero ◽  
Raffaele Addeo ◽  
Rossella De Luca ◽  
Giuseppe Lo Re ◽  
Leonardo Gulotta ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Real Life ◽  
Life Study ◽  
Heavily Pretreated ◽  
Real Life Study

scholarly journals Different Toxicity Profiles Predict Third Line Treatment Efficacy in Metastatic Colorectal Cancer Patients

2020 ◽  
Vol 9 (6) ◽  
pp. 1772
Author(s):  
Matthias Unseld ◽  
Sebastian Fischöder ◽  
Mathias Jachs ◽  
Magdalena Drimmel ◽  
Alexander Siebenhüner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Real Life ◽  
Surrogate Marker ◽  
University Hospital ◽  
Rank Test ◽  
Line Treatment ◽  
Colorectal Cancer Patients

The nucleoside trifluridine/tipiracil (TAS-102) and the multikinase inhibitor regorafenib significantly improved survival in metastatic colorectal cancer patients (mCRC). Both treatments are characterized by different treatment-related adverse events but detailed analyses of predictive side effects are rare. In this retrospective, observational, real-life study, clinical data on mCRC patients treated with trifluridine/tipiracil or regorafenib at the Medical University of Vienna, Austria and the University Hospital Zurich, Switzerland were collected. The correlation between adverse events and response or survival rates were calculated performing Fisher’s exact test and log-rank test, respectively. Common adverse events of any grade included fatigue (52%), nausea/vertigo (34%), anemia (26%), and leukopenia (22%) in trifluridine/tipiracil patients and fatigue (42%), hand-foot-skin syndrome (36%) and hoarseness (34%) in patients upon regorafenib treatment. In trifluridine/tipiracil patients the prevalence of leukopenia (p = 0.044) and weight loss (p = 0.044) was prognostic, whereas leukopenia (p = 0.044) and neutropenia (p = 0.043) predicted PFS. The disease control rate was not significantly affected. In regorafenib-treated patients, the prevalence of nausea (p = 0.001) was prognostic, while oral mucositis predicted PFS (p = 0.032) as well as the DCR (p = 0.039). In conclusion, we underline the efficacy of trifluridine/tipiracil and regorafenib in the real-life setting. We describe predictive adverse events like neutropenia/leukopenia, which might be used as surrogate marker in anticancer therapy beyond second line treatment.

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