Fruquintinib in patients with metastatic colorectal cancer failed in previously bevacizumab-based therapy: A monocentric retrospective study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15555-e15555
Author(s):  
Xiaoqiang Gu
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Safety Profile ◽  
Randomized Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Forest Plot ◽  
Lasso Regression ◽  
Standard Regimen

e15555 Background: Fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is a new targeting anti-cancer agent for refractory metastatic colorectal cancer (mCRC). Promising antitumor effect of fruquintinib monotherapy was verified in a phase III FRESCO randomized study of mCRC patients, and only 30% patients were prior bevacizumab-treated. However, comprehensive effect evaluation of fruquintinib in mCRC patients who have previously failed in bevacizumab therapy were scarce. Methods: Forty patients with metastatic CRC who had previously failed at least 2 lines of standard regimen containing bevacizumab in Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine from March 2019 to February 2020 were enrolled. These patients were administrated with fruquintinib (5mg orally, once daily) in cycles of 3 weeks on/ 1 week off. Furthermore, the primary endpoint was overall survival (OS). Secondary endpoints mainly included progression-free survival (PFS), disease control rate (DCR), objective response rate (ORR), and safety profile. Statistical analyses were performed using IBM SPSS statistics software and ‘R’ statistical software with the ‘forest plot’ package. Subsequently, the variables were screened and verified through LASSO regression with the R software “glmnet” package. Results: The mOS was 8.1months (95%CI, 5.6667-12.8667), mPFS was 4.1833 months (95% CI, 3.5333-5.0667), and DCR was 65% (26 SD in 40 patients). Particularly, gender (HR: 7.11, 95%CI:1.86-27.16,P = 0.005), age (HR:0.91, 95%CI:0.85-0.98,P = 0.012), ECOG(HR:3.75, 95%CI:1.13-12.42,P = 0.03), medication duration (HR:0.62, 95%CI:0.48-0.81,P＜0.001),and the number of metastases(HR:2.95,95%CI:1.21-7.18,P = 0.017) identified the statistically significant association with OS. Eliminating the influence of time factor, ECOG and medication cycle obtained by Lasso regression were the risk factors for OS. The most frequently reported adverse events were mainly hypertension, proteinuria, hand-foot skin reaction, fatigue and diarrhea, and any new safety signals were not observed. Conclusions: Fruquintinib showed an acceptable safety profile and promising efficacy in patients with metastatic colorectal cancer failed in previously bevacizumab-based therapy. Future studies of fruquintinib should focus on identifying the patients most likely to benefit and on minimizing toxicity.

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.

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.

Phase III Study of Weekly High-Dose Infusional Fluorouracil Plus Folinic Acid With or Without Irinotecan in Patients With Metastatic Colorectal Cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986

2005 ◽  
Vol 23 (22) ◽  
pp. 4856-4865 ◽  
Author(s):  
C.-H. Köhne ◽  
E. van Cutsem ◽  
J. Wils ◽  
C. Bokemeyer ◽  
M. El-Serafi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Folinic Acid ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Weekly Schedule ◽  
Experimental Group

Purpose To demonstrate that adding irinotecan to a standard weekly schedule of high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can prolong progression-free survival (PFS). Patients and Methods Four hundred thirty patients with measurable or assessable metastatic colorectal cancer were randomly assigned to receive either FA 500 mg/m2 as a 2-hour infusion and FU 2.6 g/m2 by intravenous 24-hour infusion, both administered weekly for 6 weeks, followed by a 2-week rest (Arbeitsgemeinschaft für Internistische Onkologie [AIO] arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m2 preceded by irinotecan 80 mg/m2 administered over 30 minutes (experimental group, n = 214). Results The median PFS time in the experimental group was 8.5 months (95% CI, 7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the AIO arm (P < .0001). The median overall survival time was increased from 16.9 to 20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to 69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO arm (P < .0001). Conclusion The addition of irinotecan to the standard AIO FU/FA regimen was associated with a highly significant improvement in PFS and response rate and was well tolerated. The results of this study confirm that irinotecan in combination with high-dose infusional FU/FA is a reference first-line treatment.

scholarly journals Chemotherapy With or Without Anti-EGFR Agents in Left- and Right-Sided Metastatic Colorectal Cancer: An Updated Meta-Analysis

2019 ◽  
Vol 17 (7) ◽  
pp. 805-811 ◽  
Author(s):  
Zi-Xian Wang ◽  
Hao-Xiang Wu ◽  
Ming-Ming He ◽  
Ying-Nan Wang ◽  
Hui-Yan Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Phase Iii ◽  
Left And Right ◽  
Meta Analyses

AbstractBackground: Previous meta-analyses have suggested primary tumor location as a predictive factor for efficacy of anti–epidermal growth factor receptor (EGFR) therapies in patients with metastatic colorectal cancer (mCRC). However, the recent phase III TAILOR trial addressing this issue was not included in those analyses. This meta-analysis incorporated data from the TAILOR trial to evaluate the efficacy of chemotherapy plus anti-EGFR agents (cetuximab [Cet] or panitumumab [Pani]) versus chemotherapy alone for RAS wild-type (wt) right- and left-sided mCRC. Patients and Methods: A PubMed-based literature search was conducted to identify randomized controlled trials (RCTs) studying the additional efficacy of Cet/Pani in combination with chemotherapy versus chemotherapy alone in RAS wt left- and right-sided mCRC. Study-level pooled analyses of hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for objective response rate (ORR) were performed. Results: Three first-line RCTs (CRYSTAL, PRIME, and TAILOR) and one second-line RCT (20050181) were included. Significant OS benefits from Cet/Pani were observed in the left-sided (HR, 0.76; 95% CI, 0.66–0.86) but not right-sided subgroups (HR, 0.99; 95% CI, 0.78–1.27). However, the addition of Cet/Pani to chemotherapy significantly improved PFS and ORR in both the left-sided (HR, 0.70; 95% CI, 0.57–0.86, and OR, 3.28; 95% CI, 1.95–5.51, respectively) and right-sided subgroups (HR, 0.76; 95% CI, 0.59–0.99, and OR, 1.78; 95% CI, 1.08–2.93, respectively). Conclusions: The addition of Cet/Pani to chemotherapy significantly benefits PFS and ORR in patients with RAS wt right-sided mCRC, indicating that anti-EGFR therapies may remain an option for selected patients.

A randomized, multicenter phase III trial of bevacizumab plus capecitabine as maintenance treatment after initial treatment with bevacizumab plus XELOX in previously untreated metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 474-474 ◽  
Author(s):  
S. Yalcin ◽  
R. Uslu ◽  
F. Dane ◽  
U. Yilmaz ◽  
N. Zengin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Maintenance Therapy ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drop Out ◽  
Phase Iii ◽  
Significance Level ◽  
Hand Foot Syndrome ◽  
Grade 3

474 Background: Colorectal cancer is one of the most frequent malignancies, second to breast cancer in women and third to lung cancer and prostate cancer in men. The aim of this study in first-line metastatic colorectal cancer (mCRC) was to achieve a better progression-free survival (PFS) and less risk of toxicity by administrating bevacizumab (BEV) + capecitabine + oxaliplatin (XELOX) for 6 cycles, stop oxaliplatin and go with maintenance therapy (BEV + capecitabine) until progression. Methods: BEV (7.5 mg/kg) + XELOX (capecitabine 1,000 mg/m2 bid d1–14 + oxaliplatin 130 mg/m2 d1 q3w) were administered until progression (Arm A) or 6 cycles of BEV + XELOX followed by BEV + capecitabine were administered until progression (Arm B). PFS was the primary endpoint; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. A sample size of 118 patients (pts) was calculated to achieve 80% power to detect an increase of 1.5 months in median PFS between Arm A (9.5 months) and Arm B (11.0 months) with a standard deviation of 3.9 months and significance level of 0.05 using a 10% drop-out rate. Results: A total of 122 pts were randomized. No significant differences were found in demographic characteristics between the two arms. Median treatment period was 6.1 (range 0.7–13.4) and 6.8 (range 0.7–12.4) months in Arms A and B, respectively. Interim analysis showed no statistically significant differences in median PFS and ORR between arms (see table). Tolerability was also acceptable in both arms with grade 3/4 diarrhoea in 7.7% vs. 8.2%, weakness in 15.2% vs. 8.4%, hand-foot syndrome in 6.3% vs. 9.4%, and neuropathy in 2.8% vs. 4.6% of pts in Arms A and B, respectively. Conclusions: BEV + capecitabine as maintenance therapy following induction BEV + XELOX is non-inferior to continuous BEV + XELOX until progression. While this study is ongoing, these interim findings suggest that maintenance therapy with BEV + capecitabine is an appropriate option following induction BEV + XELOX in pts with mCRC. [Table: see text] [Table: see text]

Cediranib Plus FOLFOX/CAPOX Versus Placebo Plus FOLFOX/CAPOX in Patients With Previously Untreated Metastatic Colorectal Cancer: A Randomized, Double-Blind, Phase III Study (HORIZON II)

2012 ◽  
Vol 30 (29) ◽  
pp. 3596-3603 ◽  
Author(s):  
Paulo M. Hoff ◽  
Andreas Hochhaus ◽  
Bernhard C. Pestalozzi ◽  
Niall C. Tebbutt ◽  
Jin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind ◽  
End Points ◽  
Significant Difference ◽  
Duration Of Response

PurposeCediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signaling with activity against all three VEGF receptors. HORIZON II [Cediranib (AZD2171, RECENTIN) in Addition to Chemotherapy Versus Placebo Plus Chemotherapy in Patients With Untreated Metastatic Colorectal Cancer] assessed infusional fluorouracil, leucovorin, and oxaliplatin/capecitabine and oxaliplatin (FOLFOX/CAPOX) with or without cediranib in patients with previously untreated metastatic colorectal cancer (mCRC).Patients and MethodsEligible patients were initially randomly assigned 1:1:1 to receive cediranib (20 or 30 mg per day) or placebo plus FOLFOX/CAPOX. In an early analysis of this and two other cediranib studies (HORIZON I [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Previously Treated Metastatic Colorectal Cancer] and HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer]), the 20-mg dose met the predefined criteria for continuation. Subsequent patients were randomly assigned 2:1 to the cediranib 20 mg or placebo arms. Progression-free survival (PFS) and overall survival (OS) were coprimary end points.ResultsIn all, 860 patients received cediranib 20 mg (n = 502) or placebo (n = 358). The addition of cediranib to FOLFOX/CAPOX resulted in PFS prolongation (hazard ratio [HR], 0.84; 95% CI, 0.73 to 0.98; P = .0121; median PFS, 8.6 months for cediranib v 8.3 months for placebo) but had no impact on OS (HR, 0.94; 95% CI, 0.79 to 1.12; P = .5707; median OS, 19.7 months for cediranib v 18.9 months for placebo). There were no significant differences in the secondary end points of objective response rate, duration of response, or liver resection rate. Median chemotherapy dose-intensity was decreased by approximately 10% in patients treated with cediranib. Adverse events (AEs) associated with cediranib were manageable.ConclusionAddition of cediranib 20 mg to FOLFOX/CAPOX resulted in a modest PFS prolongation, but no significant difference in OS. The cediranib AE profile was consistent with those from previous studies. Because of the lack of improvement in OS, cediranib plus an oxaliplatin-based regimen cannot be recommended as a treatment for patients with mCRC.

Ziv-aflibercept: A novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer

2013 ◽  
Vol 70 (21) ◽  
pp. 1887-1896 ◽  
Author(s):  
Clement Chung ◽  
Nisha Pherwani
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
Patient Response ◽  
Line Setting

Abstract Purpose The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of ziv-aflibercept in combination therapy for metastatic colorectal cancer (mCRC) are reviewed. Summary Ziv-aflibercept (Zaltrap, Regeneron Pharmaceuticals and sanofi-aventis) is a novel recombinant fusion protein that targets the angiogenesis signaling pathway of tumor cells by blocking vascular endothelial growth factor (VEGF) receptors that play a key role in tumor growth and metastasis; it is a more potent VEGF blocker than bevacizumab. Ziv-aflibercept is approved by the Food and Drug Administration for use in combination with fluorouracil, irinotecan, and leucovorin (the FOLFIRI regimen) for second-line treatment of patients with mCRC who have disease progression during first-line oxaliplatin-based chemotherapy. A Phase III trial demonstrated that relative to FOLFIRI therapy alone, the use of ziv-aflibercept was associated with significantly improved patient response, overall survival, and progression-free survival in patients with good performance status at baseline, including some who had received prior bevacizumab therapy. The most common grade 3 or 4 adverse effects associated with ziv-aflibercept use in clinical studies were neutropenia, hypertension, and diarrhea; the U.S. product labeling warns of potential hemorrhage and other treatment-related risks. Conclusion Current clinical data are insufficient to directly compare ziv-aflibercept and bevacizumab when used with standard combination chemotherapy as first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently limited to the second-line setting in combination with irinotecan-based regimens in mCRC patients who have not received irinotecan previously. The role of ziv-aflibercept in chemotherapy for other tumor types is yet to be determined.

Phase III Multicenter Randomized Trial of Oxaliplatin Added to Chronomodulated Fluorouracil–Leucovorin as First-Line Treatment of Metastatic Colorectal Cancer

2000 ◽  
Vol 18 (1) ◽  
pp. 136-136 ◽  
Author(s):  
S. Giacchetti ◽  
B. Perpoint ◽  
R. Zidani ◽  
N. Le Bail ◽  
R. Faggiuolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Phase Iii ◽  
Line Treatment ◽  
Survival Times ◽  
First Line ◽  
Grade 3 ◽  
First Line Treatment

PURPOSE: To study how adding oxaliplatin (l-OHP) to chronomodulated fluorouracil (5-FU)–leucovorin (LV) affected the objective response rate, as first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred patients from 15 institutions in four countries were randomly assigned to receive a 5-day course of chronomodulated 5-FU and LV (700 and 300 mg/m2/d, respectively; peak delivery rate at 0400 hours) with or without l-OHP on the first day of each course (125 mg/m2, as a 6-hour infusion). Each course was repeated every 21 days. Response was assessed by extramural review of computed tomography scans. RESULTS: Grade 3 to 4 toxicity from 5-FU–LV occurred in ≤ 5% of the patients (≤ 1% of the courses). Grade 3 to 4 diarrhea occurred in 43% of the patients given l-OHP (10% of the courses), and less than 2% of the patients had severe hematotoxicity. Thirteen percent of the patients had moderate functional impairment from peripheral sensory neuropathy. Sixteen percent of the patients receiving 5-FU–LV had an objective response (95% confidence interval [CI], 9% to 24%), compared with 53% of those receiving additional l-OHP (95% CI, 42% to 63%) (P < .001). The median progression-free survival time was 6.1 months with 5-FU–LV (range, 4.1 to 7.4 months) and 8.7 months (7.4 to 9.2 months) with l-OHP and 5-FU–LV (P = .048). Median survival times were 19.9 and 19.4 months, respectively. CONCLUSION: By chronomodulating 5-FU–LV, we were able to add l-OHP without compromising dose-intensities. l-OHP significantly improved the antitumor efficacy of this regimen.

Addition of Aflibercept to Fluorouracil, Leucovorin, and Irinotecan Improves Survival in a Phase III Randomized Trial in Patients With Metastatic Colorectal Cancer Previously Treated With an Oxaliplatin-Based Regimen

2012 ◽  
Vol 30 (28) ◽  
pp. 3499-3506 ◽  
Author(s):  
Eric Van Cutsem ◽  
Josep Tabernero ◽  
Radek Lakomy ◽  
Hans Prenen ◽  
Jana Prausová ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Survival Times ◽  
Previously Treated

Purpose Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. We studied the effect of adding the novel antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab. Patients and Methods Patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. The primary end point was overall survival. Results Adding aflibercept to FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) with median survival times of 13.50 versus 12.06 months, respectively. Aflibercept also significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P < .0001), with median PFS times of 6.90 versus 4.67 months, respectively. The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P = .0001). Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti–vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities. Conclusion Aflibercept in combination with FOLFIRI conferred a statistically significant survival benefit over FOLFIRI combined with placebo in patients with mCRC previously treated with oxaliplatin.

Phase III Trial of Infusional Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan (FOLFOXIRI) Compared With Infusional Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) As First-Line Treatment for Metastatic Colorectal Cancer: The Gruppo Oncologico Nord Ovest

2007 ◽  
Vol 25 (13) ◽  
pp. 1670-1676 ◽  
Author(s):  
Alfredo Falcone ◽  
Sergio Ricci ◽  
Isa Brunetti ◽  
Elisabetta Pfanner ◽  
Giacomo Allegrini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Secondary Resection ◽  
Phase Iii Study ◽  
Grade 3

Purpose The Gruppo Oncologico Nord Ovest (GONO) conducted a phase III study comparing fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI [irinotecan 165 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 200 mg/m2 day 1, fluorouracil 3,200 mg/m2 48-hour continuous infusion starting on day 1, every 2 weeks]) with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI). Methods Selection criteria included unresectable metastatic colorectal cancer, age 18 to 75 years, and no prior chemotherapy for advanced disease. The primary end point was response rate (RR). Results A total of 244 patients were randomly assigned. An increase of grade 2 to 3 peripheral neurotoxicity (0% v 19%; P < .001), and grade 3 to 4 neutropenia (28% v 50%; P < .001) were observed in the FOLFOXIRI arm. The incidence of febrile neutropenia (3% v 5%) and grade 3 to 4 diarrhea (12% v 20%) were not significantly different. Responses, as assessed by investigators, were, for FOLFIRI and FOLFOXIRI, respectively, complete, 6% and 8%; and partial, 35% and 58%, (RR, 41% v 66%; P = .0002). RR confirmed by an external panel was 34% versus 60% (P < .0001). The R0 secondary resection rate of metastases was greater in the FOLFOXIRI arm (6% v 15%; P = .033, among all 244 patients; and 12% v 36%; P = .017 among patients with liver metastases only). Progression-free survival (PFS) and overall survival (OS) were both significantly improved in the FOLFOXIRI arm (median PFS, 6.9 v 9.8 months; hazard ratio [HR], 0.63; P = .0006; median OS, 16.7 v 22.6 months; HR, 0.70; P = .032). Conclusion The FOLFOXIRI regimen improves RR, PFS, and OS compared with FOLFIRI, with an increased, but manageable, toxicity in patients with metastatic colorectal cancer with favorable prognostic characteristics. Further studies of FOLFOXIRI in combination with targeted agents and in the neoadjuvant setting are warranted.

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