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Original Investigation
May 25, 2017

FOLFOXIRI Plus Bevacizumab as Conversion Therapy for Patients With Initially Unresectable Metastatic Colorectal CancerA Systematic Review and Pooled Analysis

Author Affiliations
  • 1Oncology Unit, Oncology Department, Azienda Socio Sanitaria Territoriale Ospedale di Cremona, Cremona, Italy
  • 2Oncology Unit, Oncology Department, Azienda Socio Sanitaria Territoriale di Bergamo Ovest, Treviglio (Bergamo), Italy
  • 3Surgical Oncology Unit, Surgical Department, Azienda Socio Sanitaria Territoriale di Bergamo Ovest, Treviglio (Bergamo), Italy
JAMA Oncol. Published online May 25, 2017. doi:10.1001/jamaoncol.2017.0278
Key Points

Question  What is the efficacy of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) in terms of secondary surgical resections in patients with metastatic colorectal cancer?

Findings  In this systematic review and pooled analysis of 11 studies of FOLFOXIRI-Bev for metastatic colorectal cancer, the rate of overall surgical conversions was 39.1% and the rate of R0 surgical conversions was 28.1%; the objective response rate was 69%.

Meaning  In patients with unresectable metastatic colorectal cancer, FOLFOXIRI-Bev is associated with a significant objective response rate and a probability of surgical conversion of distant metastases approaching 40%. Overall, more than one-fourth of patients achieve an R0 resection.

Abstract

Importance  The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial.

Objective  To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions.

Data Sources  A systematic review was conducted in October 2016 in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, SCOPUS, Web of Science, Google Scholar, CINAHL, Ovid, and EMBASE using the terms FOLFOXIRI and bevacizumab and (colorectal cancer).

Study Selection  Clinical trials, retrospective case series, and prospective case series that used FOLFOXIRI-Bev for the treatment of initially unresectable metastatic colorectal cancer in humans were included. Individual case reports and retrospective case series with fewer than 10 patients were excluded.

Data Extraction and Synthesis  Data were extracted independently by 2 reviewers on a predesigned, standardized form. Ultimately, data were aggregated to obtain the pooled effect size of efficacy, according to the random-effects model and weighted for the number of patients included in each trial.

Main Outcome(s) and Measure(s)  Median overall survival and progression-free survival, overall response rates, and rates of R0 surgical conversions and overall surgical conversions.

Results  Eleven FOLFOXIRI-Bev studies published between 2010 and 2016 met the inclusion criteria and were pooled for analysis. The studies included 889 patients, with 877 patients clinically evaluable for overall response rates. The objective response rate to FOLFOXIRI-Bev was 69% (95% CI, 65%-72%; I2 = 25%). The rate of overall surgical conversions was 39.1% (95% CI, 26.9%-52.8%), and the rate of R0 surgical conversions was 28.1% (95% CI, 18.1%-40.8%). Median pooled overall survival was 30.2 months (95% CI, 26.5-33.7 months) in 6 trials with data available, and progression-free survival was 12.4 months (95% CI, 10.0-14.3 months) in 9 trials with data available. In meta-regression analysis, variables significantly associated with conversion surgery were disease limited to the liver and a higher median number of cycles (close to 12).

Conclusions and Relevance  For patients with surgically unresectable metastatic colorectal cancer, FOLFOXIRI-Bev is associated with a significant overall response rate. Such an effective regimen leads to a probability of surgical conversion of distant metastases approaching 40%, with more than one-fourth of patients having an R0 resection.

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