FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study

Iwamoto, Shigeyoshi; Takahashi, Tsuyoshi; Takahashi, Hiroshi; Nakamura, Masato; Munemoto, Yoshinori; Kato, Takeshi; Hata, Taishi; Denda, Tadamichi; Morita, Yoshitaka; Inukai, Michio; Kunieda, Katsuyuki; Nagata, Naoki; Kurachi, Kiyotaka; Ina, Kenji; Ooshiro, Mitsuru; Shimoyama, Tatsu; Baba, Hideo; Oba, Koji; Sakamoto, Junichi; Mishima, Hideyuki

doi:10.1093/annonc/mdv197

Cited by 48 publications

(22 citation statements)

References 16 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings are similar to other analyses, but the small number of comparative studies, their small size, and the reporting modality make the comparison between dose regimens difficult . The only prior study comparing low‐dose and high‐dose regimens showed no differences in terms of safety between the 2 regimens, but it should be noted that in that study patients were selected for second‐line therapy, having been previously treated with bevacizumab, potentially limiting the generalizability of that result . It would be of importance to establish the ideal bevacizumab dose that would have antitumoral effects without causing cardiovascular adverse events.…”

Section: Discussionsupporting

confidence: 76%

“…78,82,83 The only prior study comparing low-dose and high-dose regimens showed no differences in terms of safety between the 2 regimens, but it should be noted that in that study patients were selected for second-line therapy, having been previously treated with bevacizumab, potentially limiting the generalizability of that result. 84 It would be of importance to establish the ideal bevacizumab dose that would have antitumoral effects without causing cardiovascular adverse events. In vitro studies have shown that lower doses are sufficient to induce vascular normalization and that higher doses are necessary to obtain a direct cytotoxic effect.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta‐Analysis of More Than 20 000 Patients

Totzeck

Mincu

Rassaf

2017

JAHA

134

View full text Add to dashboard Cite

BackgroundThe monoclonal antibody bevacizumab effectively inhibits angiogenesis in several types of cancers by blocking vascular endothelial growth factor. However, life‐threatening cardiovascular adverse effects could limit its use and may warrant specific follow‐up strategies.Methods and ResultsWe systematically searched MEDLINE, Cochrane, EMBASE, and Web of Science for randomized controlled trials published until November 2016 that assessed patients with cancer treated with or without bevacizumab in addition to standard chemotherapy. A total of 20 050 patients with a broad range of cancer types from 22 studies were included in this analysis (10 394 in the bevacizumab group and 9656 in the control group). The risks of arterial and venous adverse events were higher in the bevacizumab groups (relative risk [RR], 1.37; 95% CI, 1.10–1.70 [P=0.004] and RR, 1.29; 95% CI, 1.12–1.47 [P<0.001], respectively), and more arterial adverse events occurred in patients taking high‐dose bevacizumab regimens. Bevacizumab treatment was associated with the highest risk of cardiac and cerebral ischemia in the high‐dose bevacizumab groups (RR, 4.4; 95% CI, 1.59–12.70 [P=0.004] and RR, 6.67; 95% CI, 2.17–20.66 [P=0.001], respectively). In addition, the risk of bleeding and arterial hypertension were higher in the bevacizumab groups (RR, 2.74; 95% CI, 2.38–3.15 [P<0.001] and RR, 4.73; 95% CI, 4.15–5.39 [P<0.00001], respectively), with higher values for patiens taking high‐dose regimens.ConclusionsTreatment with bevacizumab increases the risk of arterial adverse events, particularly cardiac and cerebral ischemia, venous adverse events, bleeding, and arterial hypertension. This risk is additionally increased with high doses of bevacizumab. Further studies should determine the appropriate options for cardio‐oncology management.Clinical Trial Registration URL: https://www.crd.york.ac.uk. Unique identifier: PROSPERO(CRD42016054305).

show abstract

Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta‐Analysis of More Than 20 000 Patients

Totzeck

Mincu

Rassaf

2017

JAHA

134

View full text Add to dashboard Cite

show abstract

“…The observed median PFS and OS in both phases of our study is consistent with the published literature, reporting that patients continue to derive benefits from bevacizumab when used beyond progression. [16][17][18] Although this study is significantly smaller than the retrospective, published, literature on NLR in other cancers, it did have enough power to detect a HR of 1.7 [10]. While our results did not prove the claim that NLR > 5 is prognostic for lower PFS [10,19], the size of the association (HR of 1.4) is consistent with data published by Chua et al [10] and other subsequent data.…”

Section: Discussionsupporting

confidence: 85%

The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]

et al. 2020

View full text Add to dashboard Cite

Background In spite of demonstrating prognostic and possibly predictive benefit in retrospective cohorts and meta-analyses of cancer populations, including colorectal cancer (CRC), prospective evaluation of the relationship between neutrophil to lymphocyte ratio (NLR) and treatment outcomes in previously untreated mCRC patients receiving bevacizumab-based therapy has not yet been performed. Methods An open-label, single arm, multi-centre study. Patients received first-line bevacizumab plus XELOX or mFOLFOX6 (Phase-A) and continued bevacizumab plus FOLFIRI beyond first progression (Phase-B). Analyses included the association of NLR with phase A progression free survival (PFS) and overall survival (OS). A sub-study investigated the safety in patients with the primary in situ tumor. An exploratory sub-study examined relationships of circulating proteomic markers with PFS. Results Phase-A enrolled 128 patients; median age was 64 years (range: 26-84), 70 (55%) were female, 71 (56%) were PS-0 and 51 (40%) had primary in situ tumor. Fifty-three (41%) patients entered Phase-B. The median baseline (b) NLR was 3.2 (range: 1.5-20.4) with 32

show abstract

“…The EAGLE trial randomized 387 patients with disease progression after oxaliplatin-based therapy with bevacizumab to second-line therapy with FOLFIRI plus either 5 or 10 mg/kg of bevacizumab. 209 No difference was seen in PFS or time to treatment failure between the arms, indicating that 5 mg/kg of bevacizumab is an appropriate dose in second-line treatment of metastatic CRC.…”

Section: Therapy After Progressionmentioning

confidence: 89%

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Benson¹,

Venook²,

Cederquist³

et al. 2017

J Natl Compr Canc Netw

725

515

View full text Add to dashboard Cite

OverviewColorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. In 2016, an estimated 95,270 new cases of colon cancer and approximately 39,220 cases of rectal cancer will occur. During the same year, an estimated 49,190 people will die of colon and rectal cancer combined. AbstractThis portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions. J Natl Compr Canc Netw 2017;15(3): 370-398 NCCN Categories of Evidence and ConsensusCategory 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate. Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate. Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

show abstract

FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study

Cited by 48 publications

References 16 publications

Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta‐Analysis of More Than 20 000 Patients

Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta‐Analysis of More Than 20 000 Patients

The prognostic role of inflammatory markers in patients with metastatic colorectal cancer treated with bevacizumab: A translational study [ASCENT]

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

Contact Info

Product

Resources

About