scholarly journals Outcome of Molecular Targeted Agents Plus Chemotherapy for Second-Line Therapy of Metastatic Colorectal Cancer: A Meta-Analysis of Randomized Trials

2016 ◽  
Vol 15 (4) ◽  
pp. e149-e156 ◽  
Author(s):  
Xueqing Pei ◽  
Yu Liu ◽  
Liwei Sun ◽  
Jun Zhang ◽  
Yuanyuan Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Second Line ◽  
Targeted Agents ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Molecular Targeted Agents

scholarly journals Optimal Sequence and Second-Line Systemic Treatment of Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Meta-Analysis

2021 ◽  
Vol 10 (21) ◽  
pp. 5166
Author(s):  
Chih-Chien Wu ◽  
Chao-Wen Hsu ◽  
Meng-Che Hsieh ◽  
Jui-Ho Wang ◽  
Min-Chi Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Second Line Therapy ◽  
Optimal Sequence ◽  
First Line Therapy ◽  
Line Therapy

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.

scholarly journals Is it necessary to add anti-angiogenic therapy to chemotherapy in patients with metastatic colorectal cancer and BRAF mutation? The systematic review and meta-analysis results

2020 ◽  
Vol 10 (2) ◽  
pp. 36-44
Author(s):  
M. Yu. Fedyanin ◽  
E. M. Polyanskaya ◽  
H. H M. Elsnukaeva ◽  
A. A. Tryakin ◽  
I. А. Pokataev ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Braf Gene ◽  
Second Line Therapy ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Line Therapy

Introduction: targeted anti‑angiogenic drugs are the integral component of systemic therapy for metastatic colorectal cancer. To date, there have been no prospective studies that would directly answer the question of the need to add anti‑ angiogenic agents to chemotherapy for BRAF‑mutated metastatic colorectal cancer. We performed a systematic review and meta‑analysis to evaluate the efficacy of adding anti‑angiogenic therapy to chemotherapy in patients with metastatic colorectal cancer harboring a mutation in the BRAF gene. Materials and methods: We searched for articles and abstracts in the PubMed, ASCO and ESMO databases, published before September 2020 and containing information on the results of prospective randomized trials comparing the combination of anti‑angiogenic agents (bevacizumab, aflibercept or ramucirumab) in the first‑or second‑line therapy for metastatic colorectal cancer, which indicate the efficacy depending on the presence of mutations in the BRAF gene. The primary endpoint was the risk ratio (RR) for progression or death with a 95 % confidence interval (95 % CI). The meta‑analysis was carried out using the Review Manager, version 5.3.Results: 4 studies met the selection criteria (AVF2107 g, AGITG MAX, VELOR and RAISE), which included data from 120 patients with the BRAF mutation, 65 (54 %) patients received a combination of chemotherapy with an anti‑angiogenic agent, and 55 (46 %) patients received only chemotherapy. The meta‑analysis showed improved progression‑free survival (RR 0.64, 95 % CI 0.4–1.02; p = 0.06; I 2 = 0 %, p for heterogeneity = 0.7; 3 studies) and overall survival (RR 0.51, 95 % CI 0.32–0.82; p = 0.005; I 2 = 0 %, p for heterogeneity = 0.54; 4 studies) in the group treated with anti‑angiogenic agents.Conclusions: the combination of chemotherapy with anti‑angiogenic agents in the first‑or second‑line therapy improves progression‑free survival and overall survival in patients with BRAF‑mutated metastatic colorectal cancer. Prospective randomized trials in this patient population are needed to determine the optimal first‑line treatment regimen.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

scholarly journals Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.

Irinotecan in Second-Line Therapy of Metastatic Colorectal Cancer

2000 ◽  
Vol 23 (4) ◽  
pp. 15-17
Author(s):  
E. Jäger ◽  
D. Jäger ◽  
J. Orth ◽  
A. Knuth
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

scholarly journals Multicenter, randomized, double-blind phase 2 trial of FOLFIRI with regorafenib or placebo as second-line therapy for metastatic colorectal cancer

Cancer ◽  
2018 ◽  
Vol 124 (15) ◽  
pp. 3118-3126 ◽  
Author(s):  
Hanna K. Sanoff ◽  
Richard M. Goldberg ◽  
Anastasia Ivanova ◽  
Seamus O'Reilly ◽  
Samer S. Kasbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Second Line ◽  
Phase 2 ◽  
Second Line Therapy ◽  
Double Blind ◽  
Phase 2 Trial ◽  
Line Therapy

scholarly journals Efficacy and safety of regorafenib as beyond second-line therapy in patients with metastatic colorectal cancer: an adjusted indirect meta-analysis and systematic review

2020 ◽  
Vol 12 ◽  
pp. 175883592094093
Author(s):  
Yinying Wu ◽  
Yangwei Fan ◽  
Danfeng Dong ◽  
Xuyuan Dong ◽  
Yuan Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Cochrane Library ◽  
Second Line ◽  
Efficacy And Safety ◽  
Line Therapy ◽  
Third Line Therapy ◽  
Third Line

Background: The evidence base for optimum third-line therapy for metastatic colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the efficacy of regorafenib as third-line therapy in mCRC. This indirect meta-analysis compared the efficacy and safety of regorafenib with other available third-line therapies for mCRC. Methods: A literature search for randomized controlled trials (RCTs) was conducted in PubMed, Embase, and Cochrane Library for studies evaluating the efficacy and safety of fruquintinib, regorafenib, TAS-102, and nintedanib as third-line therapies in patients with mCRC. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes, while objective response rate (ORR) and safety were the secondary outcomes. Hazard ratio (HR) and relative risk (RR) with their respective 95% confidence interval (CI) were used for analysis of survival, clinical response, and safety data. An adjusted indirect meta-analysis with placebo as the common comparator was performed. Results: We identified eight RCTs comparing regorafenib (two studies), fruquintinib (two studies), TAS-102 (three studies), and nintedanib (one study) against placebo. The OS with regorafenib was significantly better when compared with nintedanib (HR = 0.66; 95% CI: 0.45, 0.95, p = 0.02) but was similar to that of fruquintinib (HR = 1.01; 95% CI: 0.67, 1.52, p = 0.94) and TAS-102 (HR = 0.97; 95% CI: 0.68, 1.38, p = 0.88). The PFS and ORR for regorafenib were slightly better than those of TAS-102 (PFS: HR = 0.86, 95% CI: 0.54, 1.37, p = 0.5; ORR: RR = 1.13, 95% CI: 0.11, 11.05, p = 0.92) and nintedanib (PFS: HR = 0.68, 95% CI: 0.42, 1.10, p = 0.12; ORR: not reported) but were lower than those for fruquintinib (PFS: HR = 1.53, 95% CI: 0.93, 2.52, p = 0.08; ORR: RR = 0.68269, 95% CI: 0.045, 10.32, p = 0.79). Safety analysis showed that the RR of adverse events (AEs) was lesser in patients treated with regorafenib in comparison with that in patients treated with fruquintinib, but was similar to that in patients treated with nintedanib and TAS-102. Conclusion: Regorafenib has efficacy similar to that of TAS-102 and better safety when compared with fruquintinib. Considering the mechanism of action of regorafenib, which targets multiple factors in the angiogenic pathway, it could be an ideal option for treatment in the beyond second-line setting.

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