Faculty Opinions recommendation of Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.

2014 ◽  
Author(s):  
Sebastian Stintzing
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Study

scholarly journals Phase III study of regorafenib versus placebo as maintenance therapy in RAS wild type metastatic colorectal cancer (RAVELLO trial).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. TPS789-TPS789 ◽  
Author(s):  
Erika Martinelli ◽  
Teresa Troiani ◽  
Filippo Venturini ◽  
Andres Cervantes ◽  
Jean Yves Douillard ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Maintenance Treatment ◽  
Phase Iii ◽  
Wild Type ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Wide Range ◽  
Phase Iii Study

TPS789 Background: Treatment of metastatic colorectal cancer (mCRC) has improved due to the introduction of more active chemotherapies (CT) and novel targeted agents that have significantly increased response rate (RR), progression free survival (PFS) and overall survival (OS). Recently, CORRECT and CONCUR trials have demonstrated both activity and efficacy of regorafenib, a small multi-kinase inhibitor, as monotherapy in pretreated mCRC. The wide range of action of regorafenib makes it an ideal candidate for monotherapy in earlier disease treatment lines in which different pathways could be involved in the acquisition of resistance. To improve long term efficacy of first line therapy several therapeutic approaches of maintenance treatment have been explored in mCRC. Methods: RAVELLO is an academic randomized, double-blind, placebo-controlled, multi-center, phase III study designed to evaluate efficacy and safety of regorafenib as maintenance treatment after first line therapy. Eligible patients: pathologically confirmed mCRC RAS wild type (KRAS and NRAS genes) treated with a first line fluoropyrimidine-based CT in combination with an anti-EGFR (epidermal growth factor receptor) monoclonal antibody for a minimum of 4 to a maximum of 8 months, with a stratification by response to the first line treatment (complete response/partial response or stable disease). 480 patients will be enrolled and randomly assigned in a 1:1 ratio to receive 160 mg regorafenib or placebo per os, every day for 3 weeks of every 4 weeks cycle, until disease progression or unacceptable toxicity. Primary endpoint is PFS. With a two-tailed alpha error of 0.05, the study will have 90% power to detect a 3-month prolongation of median PFS from randomization (corresponding to a hazard ratio of progression of 0.67 with 6-month median PFS expected in the control arm). Secondary endopoint are OS, safety, and biomarker correlative studies. Currently, one patient has been enrolled and is on treatment. EudraCT number: 2013-005428-41. Clinical trial information: 2013-005428-41.

Response-Independent Survival Benefit in Metastatic Colorectal Cancer: A Comparative Analysis of N9741 and AVF2107

2008 ◽  
Vol 26 (2) ◽  
pp. 183-189 ◽  
Author(s):  
Axel Grothey ◽  
Eric E. Hedrick ◽  
Robert D. Mass ◽  
Somnath Sarkar ◽  
Sam Suzuki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Tumor Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Phase Iii Study

PurposeIn the phase III study AVF2107g, bevacizumab (BV) demonstrated a survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study, Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response.Patients and MethodsFor these retrospective, exploratory analyses, patients were defined as responders or nonresponders by whether complete or partial response was achieved with first-line therapy.ResultsCompared with IFL alone, BV plus IFL and FOLFOX each demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) regardless of objective tumor response. BV-treated nonresponders had a hazard ratio (HR) of 0.63 (P = .0001) for PFS and 0.76 (P = .0188) for OS compared with IFL-treated nonresponders. FOLFOX-treated nonresponders had an HR of 0.75 (P = .0029) for PFS and 0.74 (P = .0030) for OS compared with IFL-treated nonresponders.ConclusionIn both AVF2107g and N9741, objective response did not predict the magnitude of PFS or OS benefit from the superior therapy; nonresponders, despite a poorer prognosis than responders, achieved extended PFS and OS from BV plus IFL or FOLFOX compared with IFL. On the basis of these data, tumor response in metastatic colorectal cancer is not a necessary factor for a therapy to provide benefit to an individual patient.

Randomized Phase III Study of Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid Plus Oxaliplatin As First-Line Therapy for Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 2006-2012 ◽  
Author(s):  
Jim Cassidy ◽  
Stephen Clarke ◽  
Eduardo Díaz-Rubio ◽  
Werner Scheithauer ◽  
Arie Figer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Hand Foot Syndrome ◽  
Grade 3

PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 × 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 × 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4–containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.

Randomized, Open-Label, Phase III Study of a 28-Day Oral Regimen of Eniluracil Plus Fluorouracil Versus Intravenous Fluorouracil Plus Leucovorin as First-Line Therapy in Patients With Metastatic/Advanced Colorectal Cancer

2002 ◽  
Vol 20 (6) ◽  
pp. 1519-1526 ◽  
Author(s):  
Richard L. Schilsky ◽  
Jeremey Levin ◽  
William H. West ◽  
Alfred Wong ◽  
Bruce Colwell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Phase Iii ◽  
First Line ◽  
Open Label ◽  
First Line Therapy ◽  
Line Therapy ◽  
Open Label Phase ◽  
Phase Iii Study ◽  
Grade 3

PURPOSE: To compare the efficacy and tolerability of eniluracil (EU)/fluorouracil (5-FU) with that of 5-FU/leucovorin (LV) as first-line therapy for patients with metastatic/advanced colorectal cancer. PATIENTS AND METHODS: This multicenter, randomized, open-label, phase III study (FUMA3008) conducted in the United States and Canada compared the safety and efficacy of EU/5-FU (11.5 mg/m2/1.15 mg/m2 twice daily for 28 days every 35 days) with that of intravenous 5-FU/LV (425 mg/m2/20 mg/m2 once daily for 5 days every 28 days) in patients with previously untreated metastatic colorectal cancer. Overall survival (OS) was the primary end point. RESULTS: A total of 981 patients were randomized and 964 patients received treatment (485 EU/5FU, 479 5FU/LV). Survival for EU/5-FU was not statistically equivalent (but not statistically inferior) to that for 5-FU/LV (hazard ratio, 0.880; 95% confidence interval [CI], 0.75 to 1.03). Median duration of survival was 13.3 months in the EU/5-FU group and 14.5 months in the 5-FU/LV group. Median duration of progression-free survival for EU/5-FU was statistically inferior to that of the control group (20.0 weeks [95% CI, 19.1 to 20.9 weeks] v 22.7 weeks [95% CI, 18.3 to 24.6 weeks]; P = .01). Both treatments were well tolerated. Diarrhea was the most common nonhematologic toxicity in both groups; treatment-related grade 3 or 4 diarrhea occurred in 19% of patients treated with EU/5-FU and 16% of patients receiving 5-FU/LV (P = .354). Grade 3 or 4 granulocytopenia occurred in 5% of EU/5-FU patients and 47% of 5-FU/LV patients. CONCLUSION: Safety profiles of both treatments were acceptable. Although antitumor activity was observed, EU/5-FU did not meet the protocol-specified statistical criteria for equivalence to 5-FU/LV in terms of OS.

scholarly journals FOLFOXIRI plus bevacizumab versus FOLFOX plus bevacizumab for patients with metastatic colorectal cancer and ≥3 circulating tumour cells: the randomised phase III VISNÚ-1 trial

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e000944 ◽  
Author(s):  
Enrique Aranda ◽  
Jose Maria Viéitez ◽  
Auxiliadora Gómez-España ◽  
Silvia Gil Calle ◽  
Antonieta Salud-Salvia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Open Label ◽  
Intention To Treat ◽  
First Line Therapy ◽  
Line Therapy

Purpose5-Fluorouracil/leucovorin, oxaliplatin, irinotecan (FOLFOXIRI) plus bevacizumab is more effective than doublets plus bevacizumab as first-line therapy for metastatic colorectal cancer, but is not widely used because of concerns about toxicity and lack of predictive biomarkers. This study was designed to explore the role of circulating tumour cell (CTC) count as a biomarker to select patients for therapy with FOLFOXIRI-bevacizumab.Patients and methodsVISNÚ-1 was a multicentre, open-label, randomised, phase III study in patients with previously untreated, unresectable, metastatic colorectal carcinoma and ≥3 CTC/7.5 mL blood. Patients received bevacizumab 5 mg/kg plus FOLFOXIRI (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and 5-fluorouracil 3200 mg/m2) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 then 2400 mg/m2) by intravenous administration every 2 weeks. The primary outcome was progression-free survival (PFS).ResultsThe intention-to-treat population comprised 349 patients (FOLFOXIRI-bevacizumab, n=172; FOLFOX-bevacizumab, n=177). Median PFS was 12.4 months (95% CI 11.2 to 14.0) with FOLFOXIRI bevacizumab and 9.3 months (95% CI 8.5 to 10.7) with FOLFOX-bevacizumab (stratified HR, 0.64; 95% CI 0.49 to 0.82; p=0.0006). Grade≥3 adverse events were more common with FOLFOXIRI-bevacizumab 85.3% vs 75.1% with FOLFOX-bevacizumab (p=0.0178). Treatment-related deaths occurred in 8 (4.7%) and 6 (3.4%) patients, respectively.ConclusionsFirst-line FOLFOXIRI-bevacizumab significantly improved PFS compared with FOLFOX-bevacizumab in patients with metastatic colorectal cancer and ≥3 CTCs at baseline, which indicate a poor prognosis. CTC count may be a useful non-invasive biomarker to assist with the selection of patients for intensive first-line therapy.

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