Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
Lorenzo Antonuzzo , Giuseppe Aprile , Sandro Barni , Evaristo Maiello , Gianluca Masi , Fausto Petrelli , Luca Porcu , Mario Scartozzi , Valter Torri , Carmine Pinto
Background: Bevacizumab (BEV) improves progression-free survival (PFS) and overall survival (OS) of metastatic colorectal cancer (mCRC) patients (pts) when added to doublets in first-line setting. Yet, its use in unfit and older mCRC pts remains controversial. This systematic review and pooled-analysis evaluated the efficacy and safety data of BEV combined with first-line fluoropyrimidine monochemotherapy in unfit or elderly mCRC pts. Methods: A literature search to identify studies using first-line fluoropyrimidine monochemotherapy plus BEV in unfit pts was performed in PubMed and EMBASE databases up to May 2015. Unfit pts were selected based on age, comorbities and health status, along with monochemotherapy as the only therapeutic option. The random-effects model was used to combine the effect estimates and the I2 index to quantify the between-study heterogeneity unexplained by sampling error. Results: We screened 1,304 papers and, after a double check, 56 were considered for full text evaluation: 38 were excluded and 10 were deemed not evaluable for lack of data on unfit pts, whereas 8 (3 RCTs, 4 single arm phase II trials and 1 prospective cohort study), including 782 pts, were considered eligible for the meta-analysis. Administered monochemotherapy was capecitabine in 531 (67.9%) pts and 5-fluorouracil (5-FU) in 251 (32.1%); 500 (63.9%) pts also received BEV. Median age was 75 years, 441 (56.4%) pts were male, ECOG performance status was 0-1 in 684 (87.7%) pts. The combination with BEV produced advantages in terms of both OS (HR 0.79; 95% CI: 0.64-0.98, P = 0.03; I2= 0%) and PFS (HR 0.52; 95% CI: 0.43-0.64, P < 0.00001; I2= 0%; pooled effect estimates of RCTs have been previously reported). As expected, higher rates of all grade hypertension (27% vs 4.9%), bleeding (24% vs 6.4%), thromboembolic events (10% vs 5%) and proteinuria (25.6% vs 8.2%) were observed in the BEV combination. Conclusions: Adding BEV to first-line fluoropyrimidine monochemotherapy, either capecitabine or 5-FU, significantly improved PFS and OS in unfit and elderly pts with mCRC, with a manageable safety profile and no unexpected side effects.
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