Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest

Cremolini, Chiara; Casagrande, Mariaelena; Loupakis, Fotios; Aprile, Giuseppe; Bergamo, Francesca; Masi, Gianluca; Rocchi, Roberto; Pietrantonio, Filippo; Marmorino, Federica; Zucchelli, Gemma; Tomasello, Gianluca; Tonini, Giuseppe; Allegrini, Giacomo; Granetto, Cristina; Ferrari, Laura; Urbani, Lucio; Cillo, Umberto; Pilati, Pierluigi; Sensi, Elisa; Pellegrinelli, Alessio; Milione, Massimo; Fontanini, Gabriella; Falcone, Alfredo

doi:10.1016/j.ejca.2016.10.028

Cited by 59 publications

(41 citation statements)

References 23 publications

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“…A pooled analysis of 29 published trials indicated that the resection rate of metastases (any site) was 9.3% and the resection rate of liver metastases was 18% in FOLFIRI-Bev regimen [31]. Meanwhile, a pooled analysis of patients with liverlimited mCRC, which pooled results of three trials and showed that FOLFOXIRI-Bev had considerable R0 resection rates and survival benefits [32]. Another pooled analysis of 11 studies manifested the R0 resection rate of overall metastases and liver metastases was 28.1% and 54.7%, respectively, in FOLFOXIRI-Bev regimen [17].…”

Section: Discussionmentioning

confidence: 99%

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Lin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Conversion therapy can convert unresectable metastatic colorectal cancer (mCRC) into resectable. However, the optimal conversion regimen was not yet defined. This meta-analysis aimed to compare the efficacy and safety of the triplet chemotherapy (FOLFOXIRI) plus bevacizumab (Bev) with doublet chemotherapy (FOLFOX/FOLFIRI) plus Bev in conversion therapy. Methods: Randomized controlled trials (RCTs) from databases, including Pubmed, EMBASE, Cochrane clinical trials, clinicaltrial.gov and some conferences, were searched from the inception to November 2017. The R0 resection, objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the incidence of adverse events were pooled with the use of hazard ratio (HR) or risk ratio (RR). Results: Four RCTs with 1013 patients were included. FOLFOXIRI plus Bev regimen significantly improved the overall R0 resection rate (RR 1.41, 95% confidence interval (CI) 1.07-1.85, I²=37%), liver R0 resection rate (RR 2.28, 95% CI 1.34-3.89, I²=0%), ORR (RR 1.20, 95% CI 1.09-1.32, I²=0%), PFS (HR 0.72, 95% CI 0.62-0.84, I²=36%) and OS (HR 0.80, 95% CI 0.66-0.97, I²=0%). There was no significant difference in any Grade≥3 adverse event (RR 1.08, 95% CI 0.99-1.17, I²=0%) between two regimens. FOLFOXIRI-Bev was associated with a higher risk of neutropenia (RR 1.77, 95% CI 1.13-2.79, I²=68%) and diarrhea (RR 1.65, 95% CI 1.17-2.32, I²=0%). Conclusions: Triplet chemotherapy plus Bev significantly improved the R0 resection rates, ORR, PFS and OS in comparison with doublet chemotherapy plus Bev in conversion therapy for mCRC patients, with a higher risk of neutropenia and diarrhea.

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Section: Discussionmentioning

confidence: 99%

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Lin

et al. 2018

Cell Physiol Biochem

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“…However, most modern series report metastasectomy rates from 30% to 40% in the setting of doublet or triplet therapy when assessed by blinded reviewers and report 10% to 20% R0 resection rates. [38][39][40] Adding cetuximab or bevacizumab to a doublet chemotherapy did not meaningfully improve conversion or R0 resection rates. 27,41,42 Triplet chemotherapy combined with bevacizumab has been associated with resection rates as high as 67%.…”

Section: Chemotherapymentioning

confidence: 90%

“…The degree to which modern chemotherapy regimens render resectability is difficult to ascertain due to differences in defining “unresectable” liver metastases across studies. However, most modern series report metastasectomy rates from 30% to 40% in the setting of doublet or triplet therapy when assessed by blinded reviewers and report 10% to 20% R0 resection rates . Adding cetuximab or bevacizumab to a doublet chemotherapy did not meaningfully improve conversion or R0 resection rates .…”

Section: Chemotherapymentioning

confidence: 99%

Treatment sequencing for simultaneous colorectal liver metastases

Krell

2019

Journal of Surgical Oncology

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Up to 25% of patients with colorectal cancer present with simultaneous metastases and the liver is frequently the only metastatic site. This review will review treatment sequence planning considerations—including metastatic burden, primary tumor site, chemotherapy response, and ability to perform minimally invasive surgery—for patients with simultaneous resectable colorectal liver metastases. In addition, this review will address conversion chemotherapy, combined vs staged surgeries, and their possible sequences.

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“…Maximising tumour shrinkage increases the chances of radical resection and this is the most important variable conditioning survival independently of other prognostic factors (30)(31)(32)(33)(34)(35)(36). Nowadays, in the era of FOLFOXIRI + bevacizumab, even secondary liver resections should be considered a chance of cure for a subgroup of metastatic colorectal cancer patients with unresectable liver-limited disease (37).…”

Section: Conclusion Conclusionmentioning

confidence: 99%

The Impact of Resection Margins on the Overall and Disease-free Survival of Hepatic Colorectal Metastases

Zanghì

Cavallaro

Mongiovì

et al. 2018

SGO

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Background: Liver resection for colorectal liver metastasis (CRLM) represents a valid therapeutic option. It can offer a chance of good long-term survival, with a 5 year survival of 25-40%. Recent studies have shown that achieving a minimum of 1 cm surgical margin is not essential for long-term survival, and a microscopic free liver resection margin can be sufficient. The aim of this study is to evaluate the impact of the resection margin on recurrence, disease free survival and the overall survival. Materials and Method: All the primary liver resections with curative intention for CRLM at our surgical division between 2000 and 2010 were retrospectively reviewed. The liver resection margins were stratified according to their width. The positive and negative prognostic factors were analyzed in a univariate analysis. Results: A total of 130 patients met the study inclusion criteria. Twenty-four patients underwent major hepatectomies, while 106 patients underwent minor hepatectomies. On statistical analysis, surgical margin width (p=0.045), advanced age (p<0.001), metachronous metastasis (p=0.018) and multiple tumours (p=0.019) were associated with lower long-term survival rates. In addition, advanced age (p=0.0004), rectal tumour (p=0.004), metachronous metastases (p=0.026), multiple tumours (p=0.017), lower width in surgical margin (p=0.002) were linked to a reduced disease-free survival. Conclusion: Our study confirms that the extent of the resection margin is a powerful factor influencing prognosis after hepatectomy for CRLM. According to our experience, resection margin width is significantly associated with a higher risk of intra and extra-hepatic recurrence and less disease-free survival. However, the impossibility of achieving a resection margin greater than or equal to 10 mm should not be considered as a contraindication to surgery.

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Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest

Cited by 59 publications

References 23 publications

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal Cancer: a Meta-Analysis

Treatment sequencing for simultaneous colorectal liver metastases

The Impact of Resection Margins on the Overall and Disease-free Survival of Hepatic Colorectal Metastases

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