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.

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 .

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.

Efficacy and safety of regorafenib in combination with chemotherapy as second-line therapy in patients with metastatic colorectal cancer: A network meta-analysis.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 115-115
Author(s):  
Xiaoyu Xie ◽  
Jianwei Zhang ◽  
Huabin Hu ◽  
Yue Cai ◽  
Zehua Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Biological Agents ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
R Software

115 Background: Recent studies have shown efficacy of chemotherapy (CTX) in combination with different biological agents including regorafenib (REG) in second-line treatment of metastatic colorectal cancer (mCRC). As there is no evidence on the relative efficacy and safety of REG as compared to other biological agents in combination with CTX, we evaluated the same in this network meta-analysis (NMA). Methods: Randomized controlled trials (RCTs) comparing efficacy and safety of biological agents + CTX against CTX alone as second-line treatment of mCRC were retrieved from PubMed, EMBASE and Cochrane databases. Progression free survival (PFS) was the primary outcome, while objective response rate (ORR), overall survival (OS) and safety were secondary outcomes. Outcomes were compared by random/mixed-effects NMA using Bayesian (R software, Gemtc package) and frequentist (R software, netmeta package) approaches. Results: Twelve RCTs comparing 9 different treatment regimens with a total of 6805 patients were included for analysis. Hazard ratios (HR)/ odds ratio (OR)/ relative risk (RR) and 95% confidence intervals (CI) for PFS, ORR and grade> 3 adverse events (AE) of selected comparisons from the results of the NMA are shown in table. Conclusions: REG combined with CTX might be a potential alternative to conventional therapeutic options and could be considered as the best option for treating KRAS and BRAF mutated mCRC patients. Future RCTs are needed to confirm our results. [Table: see text]

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.

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.

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.

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 FOLFOXIRI versus FOLFOX or FOLFIRI with targeted therapy in patients with mutant BRAF metastatic colorectal cancer: A systematic review and meta-analysis

2020 ◽  
pp. 125-132
Author(s):  
M. Yu. Fedyanin ◽  
E. M. Polyanskaya ◽  
H. H.-M. Elsnukaeva ◽  
A. A. Tryakin ◽  
I. A. Pokataev ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Metastatic Colorectal Cancer ◽  
Subgroup Analysis ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Systemic Review ◽  
Free Survival

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I2 = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I2 = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I2 = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1st line for pts with mBRAF mCRC.

Efficacy and safety of regorafenib compared to TAS-102 for metastatic colorectal cancer: A systematic review and network meta-analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 735-735
Author(s):  
Ana Beatriz Kinupe Abrahao ◽  
Yoo-Joung Ko ◽  
Kelvin K. Chan ◽  
Scott R. Berry
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Objective Response ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Meta Analyses

735 Background: Recent studies have shown regorafenib and TAS-102 (TAS) to be superior to placebo (P) in refractory metastatic colorectal cancer (mCRC). However, no studies have directly compared both drugs. Giving the lack of therapeutic options for these patients,, a systematic review to compare the efficacy and safety of regorafenib compared with TAS was performed, using indirect comparison methods. Methods: A systematic review using PubMed, Medline, Embase, Scopus and Cochrane database to identify published and unpublished studies up to November 2015 for randomized controlled trials (RCTs) for patients with metastatic colorectal cancer, involving regorafenib or TAS was performed. Data including overall survival (OS), progression-free survival (PFS) and toxicity were extracted. Pairwise direct meta-analyses (regorafenib versus placebo and TAS versus placebo) and indirect comparison (regorafenib versus TAS) using network meta-analyses methods (R package “netmeta”) to preserve randomization were performed using random effects. Results: 914 citations were initially identified among which 3 RCTs fulfilled eligibility criteria (CORRECT, CONCUR and RECOURSE trials) involving 1.764 patients (regorafenib: 641, TAS: 534, Placebo: 589). Subgroups of patients (1.659) who had not received prior regorafenib or TAS-102 were used to performed meta-analyses for efficacy. In indirect comparison, there were no statically differences observed between regorafenib and TAS-102 in overall survival (HR 0.96 95% CI 0.56-1.55 p = 0.082) and progression-free survival (HR HR 0.85 95% CI 0.40-1.80 p = 0.0182). In addition, there were no differences in objective response rate and disease control between both drugs. However, regorafenib has statistically more all grade toxicity (risk difference (RD) 0.31 CI 0.25-0.38 p = 0.001) and toxicity grade 3-5 (RD 0.22 CI 0.13-0.31 p < 0.001) compared to TAS. Conclusions: In this indirect comparison, regorafenib and TAS appeared to have similar efficacy. However, regorafenib has more toxicity compared to TAS. Post-approval real world data focusing on the comparative toxicity of regorafenib and TAS is warranted.

Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study

2010 ◽  
Vol 28 (31) ◽  
pp. 4697-4705 ◽  
Author(s):  
Jean-Yves Douillard ◽  
Salvatore Siena ◽  
James Cassidy ◽  
Josep Tabernero ◽  
Ronald Burkes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
End Point

Purpose Panitumumab, a fully human anti–epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC. Patients and Methods In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status. Results KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy. Conclusion This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.

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