Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial

Masi, Gianluca; Salvatore, Lisa; Boni, Luca; Loupakis, Fotios; Cremolini, Chiara; Fornaro, Lorenzo; Schirripa, Marta; Cupini, S.; Barbara, C.; Safina, V.; Granetto, Cristina; Fea, Elena; Antonuzzo, Lorenzo; Boni, C.; Allegrini, Giacomo; Chiara, Silvana; Amoroso, Domenico; Bonetti, Andrea; Falcone, Alfredo

doi:10.1093/annonc/mdv012

Cited by 149 publications

(98 citation statements)

References 13 publications

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“…Furthermore, the concept of sustained angiogenesis inhibition in different lines of treatment for metastatic colorectal cancer patients who are not amenable to radical surgical resection proves to be effective in a series of already published works [12][13][14][15] . The virtual absence of predictive factors for efficacy/resistance further restrained wide use of this treatment opportunity.…”

Section: Discussionmentioning

confidence: 99%

Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

Salvatore¹,

Prete²,

Prochilo³

et al. 2015

JCO

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Regorafenib monotherapy is a potential option for metastatic colorectal cancer patients. However, the lack of predictive factors and the severe toxicities related to treatment have made its use in clinical practice challenging. Polymorphisms of VEGF and its receptor (VEGFR) genes might regulate angiogenesis and thus potentially influence outcome during anti-angiogenesis treatment such as regorafenib. Aim of our study was to evaluate the role of VEGF and VEGFR genotyping in determining clinical outcome for colorectal cancer patients receiving regorafenib. We retrospectively collected clinical data and samples (tumour or blood) of 138 metastatic colorectal cancer patients treated with regorafenib. We analysed the correlation of different VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs) with patients' progression-free survival (PFS) and overall survival (OS). Results from angiogenesis genotyping showed that only VEGF-A rs2010963 maintained an independent correlation with PFS and OS. Among clinical factors only ECOG PS was independently correlated with OS, whereas no correlation with PFS was evident. Grouping together those results allowed further patients stratification into 3 prognostic groups: favourable, intermediate and unfavourable. VEGF-A rs2010963 genotyping may represent an important tool for a more accurate selection of optimal candidates for regorafenib therapy.

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Section: Discussionmentioning

confidence: 99%

Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

Salvatore¹,

Prete²,

Prochilo³

et al. 2015

JCO

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“…При подгрупповом анализе не под-твердилось предикторного значения мутационного статуса гена KRAS. Однако исследование было досрочно завершено после получения результатов исследования ML18 147, в связи с чем мы и не вклю-чали данную работу в метаанализ [9].…”

Section: рис 4 Funnel Plot Demonstrating Between-study Heterogeneitunclassified

Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: a meta-analysis

Федянин¹,

Трякин²,

Тюляндин³

2018

Onkol. koloproktol.

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Objective: to assess the efficacy of anti-angiogenic agents incorporated into second-line chemotherapeutic regimens for metastatic colon cancer depending on the KRAS gene mutation status.Materials and methods. We selected completed prospective randomized controlled phase III clinical trials evaluating the efficacy of antiangiogenic agents (bevacizumab, ramucirumab and aflibercept) added to second-line chemotherapy for metastatic colon cancer with subanalysis of treatment efficacy depending on the KRAS gene mutation status. Meta-analysis was performed using the ReviewManager (RevMan) v. 5.3 (The Cochrane Collaboration, Denmark).Results. Three studies (ML18147, RAISE, VELOUR) involving 2165 patients (1137 with KRAS wild-type tumors and 1028 with KRAS-mutant tumors) met the inclusion criteria and were included into this meta-analysis. The majority of patients (84 %) received bevacizumab in the first-line treatment. The results of our meta-analysis suggest that adding an anti-angiogenic drug to chemotherapy in patients with KRAS wildtype colon cancer significantly improved both progression-free survival (hazard ratio (HR) 0.71; 95 % confidence interval (CI) 0.62–0.80; р<0.00001; I2 = 22 %, p = 0.21) and overall survival (HR 0.76; 95 % CI 0.66–0.88; р= 0.0001; I2 = 0, p = 0.59). In patients with KRASmutant colon cancer, incorporation of an anti-angiogenic drug into the treatment regimen was not associated with better overall survival (ОР0.9; 95 % CI 0.79–1.03; р= 0.11; I2 = 0, p = 0.98), although improved progression-free survival (HR 0.78; 95 % CI 0.68–0.89; р= 0.0002; I2 = 0, p = 0.46). Conclusion. Continuation of anti-angiogenic therapy in the second-line treatment for metastatic colon cancer is most effective in patients with KRAS wild-type tumors. In individuals with KRAS-mutant tumors, continuation of bevacizumab or switch to another anti-angiogenic agent in the second-line treatment improves progression-free survival and has a statistically insignificant effect on overall survival.

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“…Giantonio et al [41] ; (E3200) FOLFOX4 ± bevacizumab 7.3 vs 4.7 < 0.0001 12.9 vs 10.8 0.0011 Bennouna et al [45] ; (ML18147) Chemotherapy ± bevacizumab 5.7 vs 4.1 < 0.0001 11.2 vs 9.8 0.0062 Masi et al [46] ; (BEBYP) Chemotherapy ± bevacizumab 6. Table 2).…”

Section: P Valuementioning

confidence: 99%

Anti-angiogenic agents in metastatic colorectal cancer

Konda

Shum

Rajdev

2015

WJGO

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Colorectal cancer (CRC) is a major public health concern being the third leading cause of cancer mortality in the United States. The availability of better therapeutic options has led to a decline in cancer mortality in these patients. Surgical resection should be considered in all stages of the disease. The use of conversion therapy has made surgery a potentially curative option even in patients with initially unresectable metastatic disease. In this review we discuss the role of various antiangiogenic agents in patients with metastatic CRC (mCRC). We describe the mechanism of action of these agents, and the rationale for their use in combination with chemotherapy. We also review important clinical studies that have evaluated the safety and efficacy of these agents in mCRC patients. Despite the discovery of several promising anti-angiogenic agents, mCRC remains an incurable disease with a median overall survival of just over 2 years in patients exposed to all available treatment regimens. Further insights into tumor biology and tumor microenvironment may help improve outcomes in these patients. Core tip: Colorectal cancer is a major health concern and a leading cause of cancer mortality worldwide. New innovations have provided improved survival in recent years. In this review, we outline the novel anti-angiogenic agents and their respective roles in metastatic colorectal cancer. In addition to three agents approved by the Food and Drug Administration, several alternative anti-angiogenic agents hold promise for use in the metastatic setting.Konda B, Shum H, Rajdev L. Anti-angiogenic agents in metastatic colorectal cancer. World J Gastrointest Oncol 2015; 7(7): 71-86 Available from:

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Continuation or reintroduction of bevacizumab beyond progression to first-line therapy in metastatic colorectal cancer: final results of the randomized BEBYP trial

Abstract: This study demonstrates that the continuation or the reintroduction of bevacizumab with second-line chemotherapy beyond first progression improves the outcome and supports the use of this strategy in the treatment of mCRC. ClinicalTrials.gov number: NCT00720512.

Cited by 149 publications

References 13 publications

Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

Angiogenesis genotyping and clinical outcome during regorafenib treatment in metastatic colorectal cancer patients.

Efficacy of continuing anti-angiogenic agents in the second-line treatment for metastatic colon cancer depending on the KRAS mutation status: a meta-analysis

Anti-angiogenic agents in metastatic colorectal cancer

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