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 Safety and efficacy of panitumumab in combination with trifluridine/tipiracil for pre-treated patients with unresectable, metastatic colorectal cancer with wild-type RAS: The phase 1/2 APOLLON study

2021 ◽  
Author(s):  
Takeshi Kato ◽  
Yoshinori Kagawa ◽  
Yasutoshi Kuboki ◽  
Makio Gamoh ◽  
Yoshito Komatsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapeutic Option ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Wild Type ◽  
Open Label ◽  
Safety And Efficacy ◽  
Multicentre Phase

Abstract Background We aimed to assess the safety and efficacy of combination treatment with panitumumab plus trifluridine/tipiracil (FTD/TPI) in patients with wild-type RAS metastatic colorectal cancer (mCRC) who were refractory/intolerant to standard therapies other than anti-epidermal growth factor receptor therapy. Methods APOLLON was an open-label, multicentre, phase 1/2 trial. In the phase 1 part, 3 + 3 de-escalation design was used to investigate the recommended phase 2 dose (RP2D); all patients in the phase 2 part received the RP2D. The primary endpoint was investigator-assessed progression-free survival (PFS) rate at 6 months. Secondary endpoints included PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), time to treatment failure (TTF), and safety. Results Fifty-six patients were enrolled (phase 1, n = 7; phase 2, n = 49) at 25 Japanese centres. No dose-limiting toxicities were observed in patients receiving panitumumab (6 mg/kg every 2 weeks) plus FTD/TPI (35 mg/m2 twice daily; days 1–5 and 8–12 in a 28-day cycle), which became RP2D. PFS rate at 6 months was 33.3% (90% confidence interval [CI] 22.8–45.3). Median PFS, OS, ORR, DCR, and TTF were 5.8 months (95% CI 4.5–6.5), 14.1 months (95% CI 12.2–19.3), 37.0% (95% CI 24.3–51.3), 81.5% (95% CI 68.6–90.8), and 5.8 months (95% CI 4.29–6.21), respectively. Neutrophil count decreased (47.3%) was the most common Grade 3/4 treatment-emergent adverse event. No treatment-related deaths occurred. Conclusion Panitumumab plus FTD/TPI exhibited favourable anti-tumour activity with a manageable safety profile and may be a therapeutic option for pre-treated mCRC patients.

Safety and efficacy of first-line XELIRI with or without bevacizumab in patients with metastatic colorectal cancer: Analysis of two phase II studies.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 560-560
Author(s):  
P. Garcia-Alfonso ◽  
S. Alvarez ◽  
A. Munoz ◽  
P. Lopez ◽  
C. Riesco ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Safety Data ◽  
Patient Characteristics ◽  
First Line ◽  
Two Phase ◽  
Safety And Efficacy ◽  
Phase Ii Studies

560 Background: The safety and efficacy of first-line XELIRI (capecitabine in combination with irinotecan) and XELIRI plus bevacizumab (BEV) have been evaluated in patients with metastatic colorectal cancer (mCRC). To date, however, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy and safety data for the two regimens from separate phase II studies performed at a single institution. Methods: Patients with histologically documented metastatic or recurrent CRC and no prior treatment for advanced disease received irinotecan 175 mg/m2 on day 1 and oral capecitabine 1,000 mg/m2 twice daily on days 2-8 every 2 weeks (XELIRI study). For patients age ≥65 years, the starting doses of irinotecan and capecitabine were reduced to 140 mg/m2 and 750 mg/m2, respectively. In the second study, patients received the same regimen plus BEV 5 mg/kg on day 1 (XELIRI + BEV study). Results: A total of 53 and 46 patients were entered into the XELIRI and XELIRI + BEV studies, respectively. Patient characteristics were generally similar in both groups. Efficacy results for the ITT populations are summarized in the Table. Patients treated with XELIRI + BEV had a significantly higher ORR and longer median TTP vs. XELIRI alone and a numerically longer median OS was observed (p=NS). The overall incidence of adverse events (all grades or grade 3/4) was similar in the two groups, although alopecia, mucositis, hand–foot syndrome, and haemorrhage were more common with XELIRI + BEV vs. XELIRI alone (all p<0.05). Conclusions: In this retrospective comparison of two studies, the addition of BEV to XELIRI appeared to improve outcome relative to XELIRI alone in the first-line treatment of patients with mCRC. The overall incidence of adverse events was similar in the two groups. [Table: see text] No significant financial relationships to disclose.

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

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 630-630 ◽  
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.

Observational cohort study of first-line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Comparison of infusional FU/oxaliplatin(OX)+BV and oral FU/OX+BV.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
Kazuteru Hatanaka ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Hiraku Fukushima ◽  
Hirohito Naruse ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cohort Study ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Observational Cohort Study ◽  
Rank Test ◽  
First Line ◽  
Eligibility Criteria ◽  
Significant Difference ◽  
Observational Cohort

527 Background: A few reports have shown no difference between the efficacy of infusional FU and that of oral FU (Capecitabine/S-1) for colorectal cancer, and some studies have reported the non-inferiority between infusional FU/Oxaliplatin (OX) and oral FU/OX for metastatic colorectal cancer (mCRC). We performed a sub-group comparison between infusional FU/OX (mFOLFOX6 + BV: iFU) and oral FU/OX (CapeOX/SOX + BV: oFU) from the HGCSG0802 observational cohort study with investigated Japanese patients (pts) treated with first line BV for mCRC. Methods: The objective of HGCSG0802 was to evaluate progression-free survival (PFS), overall survival (OS), time to treatment-failure (TTF), response rate (RR), safety and so on. The key eligibility criteria of HGCSG0802 were with evaluable lesions, older than 20 years, ECOG PS 0-2, and this analysis used the cohort treated with OX-based regimens.In this analysis, pts characteristics, RR and safety were compared using Fisher’s exact test. PFS and TTF were compared using log-rank test. Results: Of 108 pts (the full analysis set), 95 pts were evaluable for treated with OX-based regimens. Forty-eight pts (50.5%) were treated with iFU and 47 pts (49.5%) were treated with oFU (CapeOX + BV 42 pts/SOX + BV 5 pts). The pts characteristics between those were generally balanced except for PS 0-1 (72.9% in iFU/93.6% in oFU; p=0.012) and synchronous liver metastases (mets) (93.8% in iFU/78.8% in oFU; p=0.040). Adverse events ≥grade 3 were balanced except for leucopenia (25.0% in iFU versus 2.1% in oFU; p=0.002) and neutropenia (43.5% in iFU and 10.9% in oFU; p=0.001). Hand-foot skin reaction was not different between two cohorts. RR was 62.5% in iFU versus 71.1% in oFU (p=0.835). The median PFS was 8.3 months in iFU versus 8.2 months in oFU (p=0.835). Conclusions: The HGCSG0802 could be a database to investigate first line BV for mCRC in clinical practice. As a result of this analysis, in Japanese daily practice, efficacy was no significant difference between infusional FU/OX and oral FU/OX, and the profiles of adverse events varied from each regimens.

Apatinib combined with Raltitrexed in patients with metastatic colorectal cancer after failure of standard therapy (AHEAD-311): A single-arm phrase II pilot trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15008-e15008
Author(s):  
Haiyan Si ◽  
Miaomiao Gou ◽  
Yong Zhang ◽  
Huan Yan ◽  
Niansong Qian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Pilot Trial ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Nausea And Vomiting ◽  
Grade 3

e15008 Background: To assess the safety and efficacy of apatinib, an oral vascular endothelial growth factor receptor-2 inhibitor, combined with thymidylate synthase inhibitor raltitrexed in patients with metastatic colorectal cancer (mCRC) as a third- or later-line therapy. Methods: Patients with mCRC after at least 2 lines of chemotherapy were enrolled whenever they previously treated with bevacizumab or not. Apatinib was given orally at 250mg or 500mg daily. Raltitrexed was administered intravenously at 3 mg/m2 on day 1 every 3 weeks. The primary endpoints were progression-free survival (PFS). The second endpoints were objective response rate (ORR), overall survival (OS) and safety. Results: From August 2017 to November 2018, thirty-one patients were enrolled in Chinese PLA General Hospital. After a median follow-up of 6.4 months, the median treatment cycle was 4. four patient achieved partial response(PR), and 11 patients achieved stable disease (SD) and 16 achieved progression disease (PD) in accordance with RECIST version 1.0, illustrating a DCR of 48.4% and an ORR of 12.9% .The Median PFS was 2.4 months and the median OS was 6.4 months. The most common adverse events were hypertension (n=12, 38.7%), nausea and vomiting (n=11, 33.8%), myelosuppression (n=9, 29.0%). The most common grade 3 to 4 adverse events were hypertension (n=2, 6.4%) and hand-foot syndrome (n=2, 6.4%). Grade 3 to 4 hematologic toxicities were rare. One patient died from cardiac arrest after three days treatment. There was no significantly association between PFS or OS, and clinical features including tumor location, KRAS status, and prior surgery or not, and number of metastatic organs. There was no trend showing patients who experienced had hypertension or myelosuppression had longer PFS and OS. Compared to the patients never received bevacizumab, the patients who had previously bevacizumab had the similar PFS and OS (3.9 versus 2.3months, P=0.787; 6.1 versus 6.4months, P=0.287). Grade1-2 nausea and vomiting and age <57 were independent predictors for longer PFS and OS. Conclusions: Apatinib combined with raltitrexed had efficacy but had limited survival benefit in mCRC refractory to standard chemotherapy. This regime showed us a higher risk of adverse event incidence and warrant further exploring of benefit population. Clinical trial information: NCT03344614 .

Prognostic impact of immune-related adverse events with nivolumab in patients with advanced gastric cancer: A multicenter retrospective analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 347-347
Author(s):  
Yuno Ohya ◽  
Takayuki Ando ◽  
Akira Ueda ◽  
Kohei Ogawa ◽  
Iori Motoo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Practice ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Retrospective Analysis ◽  
Prognostic Impact ◽  
Significant Difference ◽  
Metastatic Sites ◽  
Practice Methods ◽  
Ecog Ps

347 Background: Nivolumab was established as one of the standard treatments for previously treated advanced gastric cancer (AGC). The aim of this study is to evaluate the frequency of immune-related adverse events (irAEs) with Nivolumab and its impact on treatment efficacy in clinical practice. Methods: We performed multicenter retrospective analysis, which included 90 patients with advanced gastric cancer who received Nivolumab treatment between October 2017 and September 2019. The frequency of irAEs and its treatment outcome were evaluated, and survival was compared during Nivolumab treatment. Results: The characteristics of 90 patients in this analysis were as follows: median age (range), 68 (36-85); male/female, 56/34; ECOG PS 0-1/≥2, 62/28; number of metastatic sites 1/≥2, 36/56; treatment line 3/≥4, 63/27. Median treatment cycle of nivolumab treatment was 3 (range 1-26). The overall response in 68 patients with target lesions was 6.3% (4/68), and the median PFS and OS was 1.5 and 4.3 months, respectively. IrAEs were observed in 8 patients (8.8%), including grade 4 pneumonitis, grade 2 or 3 adrenal insufficiency, and grade 2 hypothyroidism, encephalitis, and immune thrombocytopenia. Median time to onset of irAEs was 1.3 (range 0.6-10.5) months. Six were treated with systemic corticosteroid therapy, and all irAEs were relieved. The median PFS and OS were 4.7 months (95%CI, 1.2-9.3) and 12.2 months (95% CI, 3.2-not reached) in patient with irAEs, and 1.4 months (95%CI, 1.1-1.9) and 4.1 months (95%CI, 2.6-6.6) in those without, respectively. There was significant difference in the PFS (p=0.005) and OS (p=0.03). Conclusions: Nivolumab was effective and well tolerated even in clinical practice. Development of irAEs may be associated with better outcome of Nivolumab in patients with AGC.

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

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052092640
Author(s):  
Guan-Li Su ◽  
Yuan-Yuan Wang ◽  
Jin-Cheng Wang ◽  
Hao Liu
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Similar Efficacy ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Hand Foot Syndrome

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.

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.

Sign in / Sign up

Export Citation Format

Share Document