Anti-VEGF and Anti-EGFR Monoclonal Antibodies in the First-line Therapy for Metastatic Colorectal Cancer - A Meta-Analysis

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.

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Tumor sidedness and efficacy of first-line therapy in patients with RAS/BRAF wild-type metastatic colorectal cancer: A network meta-analysis

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2019.102823 ◽

2020 ◽

Vol 145 ◽

pp. 102823

Author(s):

Chih-Chien Wu ◽

Jui-Ho Wang ◽

Pei-Chin Lin ◽

Chun-An Liang ◽

Ching-Ying Huang ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Wild Type ◽

First Line ◽

First Line Therapy ◽

Line Therapy

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Impact of Delayed Addition of Anti-EGFR Monoclonal Antibodies on the Outcome of First-Line Therapy in Metastatic Colorectal Cancer Patients: a Retrospective Registry-Based Analysis

Targeted Oncology ◽

10.1007/s11523-018-0597-7 ◽

2018 ◽

Vol 13 (6) ◽

pp. 735-743 ◽

Cited By ~ 2

Author(s):

Ondrej Fiala ◽

Veronika Veskrnova ◽

Renata Chloupkova ◽

Alexandr Poprach ◽

Igor Kiss ◽

...

Keyword(s):

Colorectal Cancer ◽

Monoclonal Antibodies ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Colorectal Cancer Patients

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Cetuximab-based or bevacizumab-based first-line treatment in patients with KRAS p.G13D mutated metastatic colorectal cancer (mCRC)? A meta-analysis of 54 cases.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.511 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 511-511 ◽

Cited By ~ 1

Author(s):

Volker Heinemann ◽

Anke Reinacher-Schick ◽

Sebastian Stintzing ◽

Clemens Albrecht Giessen ◽

Andrea Tannapfel ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Progression Free Survival ◽

Pooled Analysis ◽

Line Treatment ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

First Line Treatment

511 Background: KRAS p.G13D mutant metastatic colorectal cancer (mCRC) has been identified to represent a cetuximab-sensitive subtype of KRAS mutant mCRC. This analysis aims to answer the question whether first-line treatment of p.G13D mCRCs should contain cetuximab or bevacizumab. Methods: Fifty-four patients with p.G13D mutant mCRC were pooled in this analysis. All patients underwent systemic 1st-line treatment with a fluoropyrimidine and oxaliplatin/irinotecan that was combined with either cetuximab or bevacizumab. Results: Overall response rate was comparable between cetuximab- and bevacizumab-based regimens (58% vs 57%). Progression-free survival was comparable (8.0 months-cetuximab-group vs 8.7 months bevacizumab-group). Overall survival (OS) was longer in patients treated with cetuximab as first-line therapy (20.1 months vs 14.9 months). Logistic regressions modelling OS revealed oxaliplatin-based first-line treatment to correlate significantly with poor outcome (p=0.03). Moreover, a strong trend in favour of capecitabine compared to infusional 5-FU (p=0.06) was seen.. Responders among our cohort showed a benefit concerning PFS and OS undergoing cetuximab- but not bevacizumab-based regimen. Conclusions: This retrospective pooled analysis suggests that cetuximab-based first-line therapy in p.G13D mutant mCRC shows similar activity compared to bevacizumab-containing regimen. Infusional 5-FU and oxaliplatin may represent inferior options compared to capecitabine and irinotecan in p.G13D mutant mCRC 1st-line treatment.

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Comparison of irinotecan and oxaliplatin as the first-line therapies for metastatic colorectal cancer: a meta-analysis

BMC Cancer ◽

10.1186/s12885-021-07823-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sadayuki Kawai ◽

Nozomi Takeshima ◽

Yu Hayasaka ◽

Akifumi Notsu ◽

Mutsumi Yamazaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Controlled Trials ◽

Significant Heterogeneity ◽

Cochrane Central Register ◽

First Line ◽

Anti Vegf ◽

Significant Difference ◽

High Incidence

Abstract Background Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC. Methods This meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results Nineteen trials involving 4571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS (pooled HR = 0.91, 95% CI = 0.80–1.03, P = 0.15). Conclusion Although the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. The combination of anti-VEGF antibody and IRI was associated with better PFS compared with anti-VEGF antibody and Ox. Both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.

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