Efficacy and Safety of Bevacizumab Combined With Fluoropyrimidine Monotherapy for Unfit or Older Patients With Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.
Whether bevacizumab represents a feasible option for the first-line treatment of unfit and elderly patients with metastatic colorectal cancer (mCRC) remains controversial. The present systematic review and meta-analysis evaluated the efficacy and safety data of bevacizumab combined with first-line fluoropyrimidine monochemotherapy for these complex patients.



A systematic search of the published data was conducted through May 31, 2016. The random-effects model was used to combine the effect estimates and the I2index to quantify the between-study heterogeneity unexplained by sampling error.



We included 3 randomized controlled trials, 4 single-arm phase II trials, and 1 prospective cohort study in the present meta-analysis (n = 782). The monochemotherapy administered was capecitabine in 531 patients (67.9%) and 5-fluorouracil in 251 (32.1%); 500 (63.9%) also received bevacizumab. The median age was 75 years, 441 patients (56.4%) were men, and the Eastern Cooperative Oncology Group performance status was 0 to 1 in 684 patients (87.7%). The combination with bevacizumab produced advantages in terms of both progression-free survival (hazard ratio, 0.52; 95% confidence interval, 0.43-0.64; P < .00001; I2= 0%) and overall survival (HR, 0.79; 95% CI, 0.64-0.98; P = .03; I2= 0%). The pooled effect estimates of the randomized controlled trials have been previously reported. As expected, 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 more frequent in the bevacizumab combination group.



Adding bevacizumab to first-line fluoropyrimidine monochemotherapy significantly improved progression-free and overall survival in unfit and elderly patients with mCRC, with a manageable safety profile and no unexpected toxicities.
Department of Medical Oncology, Istituto di Ricovero e Cura a Carattere Scientifico-Arcispedale S. Maria Nuova, Reggio Emilia, Italy. Electronic address: pinto.carmine@asmn.re.it.
Carmine
C
Pinto
Department of Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
Lorenzo
L
Antonuzzo
Department of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Luca
L
Porcu
Department of Medical Oncology, University and General Hospital, Udine, Italy.
Giuseppe
G
Aprile
Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Evaristo
E
Maiello
Division of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
Gianluca
G
Masi
Oncology Unit, Azienda Ospedaliera Treviglio, Treviglio, Italy.
Fausto
F
Petrelli
Department of Oncology, Università di Cagliari-Azienda Ospedaliero Universitaria, Monserrato, Italy.
Mario
M
Scartozzi
Department of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Valter
V
Torri
Oncology Unit, Azienda Ospedaliera Treviglio, Treviglio, Italy.
Sandro
S
Barni
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab / Q000008:administration & dosage; D000069287:Capecitabine / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil
Chemotherapy; Elderly; First-line; Overall survival; Progression-free survival