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.

scholarly journals Phase II study of lenvatinib for metastatic colorectal cancer refractory to standard chemotherapy: the LEMON study (NCCH1503)

ESMO Open ◽  
2020 ◽  
Vol 5 (4) ◽  
pp. e000776 ◽  
Author(s):  
Satoru Iwasa ◽  
Natsuko Okita ◽  
Aya Kuchiba ◽  
Gakuto Ogawa ◽  
Mamiko Kawasaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Growth Factor ◽  
Disease Control ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Vegf Receptor ◽  
Free Survival

BackgroundLenvatinib inhibits tyrosine kinases, including vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor alpha, RET proto-oncogene and KIT proto-oncogene, receptor tyrosine kinase. We assessed the efficacy and safety of lenvatinib in patients with metastatic colorectal cancer after failure of standard chemotherapies.Patients and methodsThis was an open-label, single centre, single-arm, phase 2 study. Eligible patients had unresectable metastatic colorectal adenocarcinoma, refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, trifluridine/tipiracil, anti-VEGF therapy and anti-epidermal growth factor receptor therapy (for tumours with wild-type RAS). Patients were treated with oral lenvatinib at 24 mg one time a day in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was centrally assessed disease control rate. Secondary endpoints included safety, response rate, progression-free survival and overall survival. The planned sample size was 30 patients to expect a disease control rate of 60% with a threshold disease control rate of 35%, one-sided alpha of 5% and power of 80%ResultsBetween 24 October 2016 and 23 January 2018, 30 patients were enrolled; 11 (37%) and 19 (63%) had received 3 or ≥4 lines of prior chemotherapy for metastatic disease, respectively. The median number of lenvatinib cycles was 4 (range 1–13). The centrally assessed disease control rate was 70.0% (21/30, 90% CI 53.5% to 83.4%, one-sided p=0.0001); 2 patients had a partial response and 19 had a stable disease. Median progression-free survival was 3.6 months (95% CI 2.6 to 3.7). Median overall survival was 7.4 months (95% CI 6.4 to 10.8). The most common grade ≥3 adverse events were hypertension (53%), thrombocytopenia (10%), increased alanine aminotransferase and anorexia (7% each).ConclusionsLenvatinib showed promising clinical activity and was tolerated in patients with metastatic colorectal cancer after failure of standard chemotherapies.Trial registration numberUMIN-CTR, UMIN000023446 and JAMCCT-CTR, JMA-IIA00261.

scholarly journals Bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer

2010 ◽  
Vol 14 (Suppl 2) ◽  
pp. 47-53
Author(s):  
S Whyte ◽  
A Pandor ◽  
M Stevenson ◽  
A Rees
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Absolute Difference ◽  
First Line ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one phase III, multicentre, multinational, randomised, open-label study (NO16966 trial). This two-arm study was originally designed to demonstrate the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil plus folinic acid plus oxaliplatin (FOLFOX)-4 in adult patients with histologically confirmed metastatic colorectal cancer who had not previously been treated. Following randomisation of 634 patients, the open-label study was amended to include a 2 × 2 factorial randomised (partially blinded for bevacizumab) phase III trial with the coprimary objective of demonstrating superiority of bevacizumab in combination with chemotherapy compared with chemotherapy alone. Measured outcomes included overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life. The manufacturer’s primary pooled analysis of superiority (using the intention-to-treat population) showed that after a median follow-up of 28 months, the addition of bevacizumab to chemotherapy significantly improved progression-free survival and overall survival compared with chemotherapy alone in adult patients with histologically confirmed metastatic colorectal cancer who were not previously treated [median progression-free survival 9.4 vs 7.7 months (absolute difference 1.7 months); hazard ratio (HR) 0.79, 97.5% confidence interval (CI) 0.72 to 0.87; p = 0.0001; median overall survival 21.2 vs 18.9 months (absolute difference 2.3 months); HR 0.83, 97.5% CI 0.74 to 0.93; p = 0.0019]. The NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free survival and overall survival when bevacizumab was added to XELOX or FOLFOX. However, the size of the actual treatment effect of bevacizumab is uncertain. The ERG believed that the modelling structure employed was appropriate, but highlighted several key issues and areas of uncertainty. At the time of writing, NICE was yet to issue the guidance for this appraisal.

scholarly journals Efficacy of Panitumumab and Cetuximab in Patients with Colorectal Cancer Previously Treated with Bevacizumab; a Combined Analysis of Individual Patient Data from ASPECCT and WJOG6510G

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1715
Author(s):  
Hiroya Taniguchi ◽  
Takeharu Yamanaka ◽  
Daisuke Sakai ◽  
Kei Muro ◽  
Kentaro Yamazaki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Clinical Trial Registration ◽  
Cox Models ◽  
Exon 2 ◽  
Free Survival ◽  
Previously Treated

Background: Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. Methods: The subgroup that received bevacizumab either prior to panitumumab or cetuximab monotherapy (ASPECCT) or in combination with irinotecan (WJOG6510G) was included. Multivariate Cox models were created, including the treatment arms as covariates together with patient, disease and treatment characteristics. Results: We included 185 and 189 patients in the panitumumab and cetuximab arms, respectively. The median overall survival was 12.8 and 10.1 months [p = 0.0031; log-rank test, stratified by trial; hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90], and the median progression-free survival was 4.7 and 4.1 months, in the panitumumab and cetuximab arms, respectively (p = 0.0207; HR, 0.79; 95% CI, 0.64–0.97). The treatment regimen was an independent prognostic factor of overall survival (adjusted HR, 0.69; 95% CI, 0.54–0.87; p = 0.0013). Conclusions: Panitumumab significantly prolonged the overall survival and progression-free survival, when compared with cetuximab in the cohort that previously received bevacizumab in the included studies. Clinical Trial Registration: ASPECCT trial registered with ClinicalTrials.gov (NCT01001377) and WJOG6510G trial registered with UMIN-CTR (UMIN000006643).

scholarly journals Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic Review

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Amartej Merla ◽  
Sanjay Goel
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
The United States ◽  
Targeted Agents ◽  
The Future ◽  
Epidermal Growth

Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR)) and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF)), has improved the median survival of patients with metastatic colorectal cancer to around 24 months. Clearly, better and more efficacious drugs are needed, and target-specific agents remain the future of cancer treatment. On this front, rapid advances are being made, which are likely to change the future of the management of metastatic colorectal cancer. However, absence of specific biomarkers for the use of targeted agents, in the subset of population who will benefit from the treatment, remains a major drawback. In this paper, we review agents that are in phases 1 and 2 clinical development, specifically targeting the EGFR and its subsequent downstream pathways.

On-treatment progression-free survival analysis of ziv-aflibercept/FOLFIRI treatment within 28 days of end of treatment in metastatic colorectal cancer: Updated efficacy results from the VELOUR study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3573-3573
Author(s):  
David Ferry ◽  
Tae Won Kim ◽  
Tormod Kyrre Guren ◽  
Jayesh Desai ◽  
Luis Marcelo Villanueva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Rank Test ◽  
Free Survival

3573 Background: The phase III VELOUR study demonstrated that adding the novel antiangiogenic agent ziv-aflibercept (known as aflibercept outside the United States) to FOLFIRI in patients with metastatic colorectal cancer previously treated with oxaliplatin significantly improved overall survival, progression-free survival (PFS), and overall response rate vs placebo/FOLFIRI. We performed an additional analysis of PFS “on-treatment,” censoring events that occurred more than 28 days after last treatment dose. Methods: Patients were randomized to receive ziv-aflibercept 4 mg/kg or placebo every 2 weeks in combination with FOLFIRI. An independent review committee determined progression based on radiologic review. PFS was estimated using Kaplan-Meier analysis, with censoring of events after the last dose plus 28 days. Treatment groups were compared using a log-rank test and were stratified by Eastern Cooperative Oncology Group performance status and prior bevacizumab therapy. Hazard ratio (HR) and confidence interval (CI) were estimated using a Cox proportional hazard model. Results: On-treatment analysis showed significantly increased PFS for patients treated with ziv-aflibercept/FOLFIRI compared with placebo/FOLFIRI (Table). More patients were censored in the ziv-aflibercept arm due to adverse events. Conclusions: The on-treatment PFS analysis demonstrates a significantly improved treatment effect of the addition of ziv-aflibercept to FOLFIRI (HR=0.55) over what was observed in the primary analysis suggesting that continuing treatment with ziv-aflibercept up to disease progression provides additional benefit. Clinical trial information: NCT00561470. [Table: see text]

EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients With Metastatic Colorectal Cancer

2008 ◽  
Vol 26 (14) ◽  
pp. 2311-2319 ◽  
Author(s):  
Alberto F. Sobrero ◽  
Joan Maurel ◽  
Louis Fehrenbacher ◽  
Werner Scheithauer ◽  
Yousif A. Abubakr ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Study Groups ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Open Label ◽  
Number Of Patients ◽  
Post Trial

PurposeTo determine whether adding cetuximab to irinotecan prolongs survival in patients with metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine and oxaliplatin.Patients and MethodsThis multicenter, open-label, phase III study randomly assigned 1,298 patients with epidermal growth factor receptor–expressing mCRC who had experienced first-line fluoropyrimidine and oxaliplatin treatment failure to cetuximab (400 mg/m2day 1 followed by 250 mg/m2weekly) plus irinotecan (350 mg/m2every 3 weeks) or irinotecan alone. Primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR), and quality of life (QOL).ResultsMedian OS was comparable between treatments: 10.7 months (95% CI, 9.6 to 11.3) with cetuximab/irinotecan and 10.0 months (95% CI, 9.1 to 11.3) with irinotecan alone (hazard ratio [HR], 0.975; 95% CI, 0.854 to 1.114; P = .71). This lack of difference may have been due to post-trial therapy: 46.9% of patients assigned to irinotecan eventually received cetuximab (87.2% of those who did, received it with irinotecan). Cetuximab added to irinotecan significantly improved PFS (median, 4.0 v 2.6 months; HR, 0.692; 95% CI, 0.617 to 0.776; P ≤ .0001) and RR (16.4% v 4.2%; P < .0001), and resulted in significantly better scores in the QOL analysis of global health status (P = .047). Cetuximab did not exacerbate toxicity, except for acneform rash, diarrhea, hypomagnesemia, and associated electrolyte imbalances. Neutropenia was the most common severe toxicity across treatment arms.ConclusionCetuximab and irinotecan improved PFS and RR, and resulted in better QOL versus irinotecan alone. OS was similar between study groups, possibly influenced by the large number of patients in the irinotecan arm who received cetuximab and irinotecan poststudy.

scholarly journals Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E–Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study

2019 ◽  
Vol 37 (17) ◽  
pp. 1460-1469 ◽  
Author(s):  
Eric Van Cutsem ◽  
Sanne Huijberts ◽  
Axel Grothey ◽  
Rona Yaeger ◽  
Pieter-Jan Cuyle ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Phase Iii ◽  
Cancer Trial ◽  
Free Survival

PURPOSE To determine the safety and preliminary efficacy of selective combination targeted therapy for BRAF V600E–mutant metastatic colorectal cancer (mCRC) in the safety lead-in phase of the open-label, randomized, three-arm, phase III BEACON Colorectal Cancer trial ( ClinicalTrials.gov identifier: NCT02928224; European Union Clinical Trials Register identifier: EudraCT2015-005805-35). PATIENTS AND METHODS Before initiation of the randomized portion of the BEACON Colorectal Cancer trial, 30 patients with BRAF V600E–mutant mCRC who had experienced treatment failure with one or two prior regimens were to be recruited to a safety lead-in of encorafenib 300 mg daily, binimetinib 45 mg twice daily, plus standard weekly cetuximab. The primary end point was safety, including the incidence of dose-limiting toxicities. Efficacy end points included overall response rate, progression-free survival, and overall survival. RESULTS Among the 30 treated patients, dose-limiting toxicities occurred in five patients and included serous retinopathy (n = 2), reversible decreased left ventricular ejection fraction (n = 1), and cetuximab-related infusion reactions (n = 2). The most common grade 3 or 4 adverse events were fatigue (13%), anemia (10%), increased creatine phosphokinase (10%), increased AST (10%), and urinary tract infections (10%). In 29 patients with BRAF V600E–mutant tumors (one patient had a non– BRAF V600E–mutant tumor and was not included in the efficacy analysis), the confirmed overall response rate was 48% (95% CI, 29.4% to 67.5%), median progression-free survival was 8.0 months (95% CI, 5.6 to 9.3 months), and median overall survival was 15.3 months (95% CI, 9.6 months to not reached), with median duration of follow-up of 18.2 months (range, 16.6 to 19.8 months). CONCLUSION In the safety lead-in, the safety and tolerability of the encorafenib, binimetinib, and cetuximab regimen is manageable and acceptable for initiation of the randomized portion of the study. The observed efficacy is promising compared with available therapies and, if confirmed in the randomized portion of the trial, could establish this regimen as a new standard of care for previously treated BRAF V600E–mutant mCRC.

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.

Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study

2008 ◽  
Vol 26 (12) ◽  
pp. 2013-2019 ◽  
Author(s):  
Leonard B. Saltz ◽  
Stephen Clarke ◽  
Eduardo Díaz-Rubio ◽  
Werner Scheithauer ◽  
Arie Figer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Placebo Group ◽  
Metastatic Colorectal Cancer ◽  
Disease Progression ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival

PurposeTo evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).Patients and MethodsPatients with MCRC were randomly assigned, in a 2 × 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS).ResultsA total of 1,401 patients were randomly assigned in this 2 × 2 analysis. Median progression-free survival (PFS) was 9.4 months in the bevacizumab group and 8.0 months in the placebo group (hazard ratio [HR], 0.83; 97.5% CI, 0.72 to 0.95; P = .0023). Median overall survival was 21.3 months in the bevacizumab group and 19.9 months in the placebo group (HR, 0.89; 97.5% CI, 0.76 to 1.03; P = .077). Response rates were similar in both arms. Analysis of treatment withdrawals showed that, despite protocol allowance of treatment continuation until disease progression, only 29% and 47% of bevacizumab and placebo recipients, respectively, were treated until progression. The toxicity profile of bevacizumab was consistent with that documented in previous trials.ConclusionThe addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved PFS in this first-line trial in patients with MCRC. Overall survival differences did not reach statistical significance, and response rate was not improved by the addition of bevacizumab. Treatment continuation until disease progression may be necessary in order to optimize the contribution of bevacizumab to therapy.

On-treatment progression-free survival analysis of aflibercept-FOLFIRI treatment within 28 days of progression in metastatic colorectal cancer: Updated efficacy results from the VELOUR study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 469-469 ◽  
Author(s):  
David Raymond Ferry ◽  
Tae Won Kim ◽  
Tormod Kyrre Guren ◽  
Jayesh Desai ◽  
Luis Marcelo Villanueva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Rank Test ◽  
Primary Analysis ◽  
Ecog Performance Status ◽  
Free Survival

469 Background: The phase III VELOUR study demonstrated that adding the novel antiangiogenic agent aflibercept (known as ziv-aflibercept in the United States) to FOLFIRI in patients with metastatic colorectal cancer previously treated with oxaliplatin significantly improved overall survival, progression-free survival (PFS), and overall response rate versus placebo-FOLFIRI. We performed an additional analysis of PFS “on-treatment,” censoring events that occurred more than 28 days after last treatment dose. Methods: Patients were randomized to receive aflibercept 4 mg/kg or placebo every 2 weeks in combination with FOLFIRI. An independent review committee determined progression based on radiologic review. PFS was estimated using Kaplan-Meier analysis, with censoring of events after the last dose plus 28 days. Treatment groups were compared using a log-rank test stratified by ECOG performance status and prior bevacizumab therapy. Hazard ratio (HR) and confidence interval (CI) were estimated using a Cox proportional hazard model. Results: On-treatment PFS results are shown in the Table. Patients on aflibercept-FOLFIRI showed significantly increased on-treatment PFS compared with patients on placebo-FOLFIRI. More patients were censored in the aflibercept arm due to adverse events, thus decreasing the number of events. Conclusions: On-treatment PFS with aflibercept-FOLFIRI was significantly increased compared with placebo-FOLFIRI, which is consistent with the PFS benefit observed in the primary analysis. Clinical trial information: NCT00561470. [Table: see text]

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