Treatment of Colorectal Cancer with and without Bevacizumab: A Phase III Study

Abstract

Objective: The objective of this phase III trial was to compare chemotherapy combined with bevacizumab versus chemotherapy alone in the treatment of patients with advanced colorectal cancer. Methods: From September 2004 till September 2008, 222 treatment-naive patients were enrolled and divided into 2 arms: 114 arm A patients were treated with leucovorin, 5-fluorouracil plus irinotecan in combination with bevacizumab, and 108 arm B patients were treated as above without bevacizumab. All patients were stage IV with histologically confirmed adenocarcinoma. Results: The median overall survival of arm A patients was 22.0 months (95% CI: 18.1–25.9) and 25.0 months (CI: 18.1–31.9) for arm B patients. There was no statistically significant difference between the 2 arms (p = 0.1391). No statistically significant difference between the 2 arms regarding the response ratewas observed: partial response, 42 patients (36.8%) and 38 patients (35.2%) for arms A and B, respectively. Hematologic toxicity did not differ in the comparison of the 2 arms. Nonhematologic toxicity in arm A involved hypertension in 23 (20.2%) of the patients and proteinuria in 7 (6.1%); 3 patients experienced hemorrhage and 1 patient intestinal perforation. None of these side effects was observed in arm B patients. Conclusion: No statistically significant difference in median overall survival in patients with advanced colorectal cancer treated with bevacizumab plus a combination therapy (arm A) and those treated with the combination only, without bevacizumab (arm B), was observed.

The Efficacy of Additional Bevacizumab to Cytotoxic Chemotherapy Regimens for the Treatment of Colorectal Cancer: An Updated Meta-Analysis for Randomized Trials

“…Two trials 22,23 underwent FLU + LEU based chemotherapy, with 349 patients involved; 3 trials 10,25-29 underwent IFL-based chemotherapy, with 1,249 patients involved; 3 trials 15,[30][31][32] underwent FOLFOX based chemotherapy, with 3,834 patients involved; 1 trial underwent CAP based 33,34 chemotherapy, with 313 patients involved; 1 trial 35 underwent both CAP + OXA based and FOLFOX based chemotherapy, with 700 patients involved, respectively. Seven trials 10,15,[22][23][24][25][26][27][30][31][32] were completed in USA, the other three trials were completed in Greece, 28 China 29 and Australia, 33,34 respectively. In meta-analyses done for OS and PFS when comparing targeted agent-BEV added to CTX versus CTX alone in the treatment of CRC, BEV is associated with evidently decreased HR [ Fig.…”

“…Subgroup analyses were done basing on different CTX, significantly decreased HRs for subtotal effects in OS were identified in the regimens about FLU + LEU based and FOLFOX based chemotherapies with/without BEV, with no evidence of statistical heterogeneity; while no significant differences were identified between CAP based chemotherapy with/ without BEV (with no heterogeneity was identified) and IFL based chemotherapy with/without BEV, but with evidence of statistical heterogeneity (I 2 = 80.1%, p = 0.007) in IFL group. Sensitivity analyses were performed, and statistical heterogeneity disappeared after eliminating trial 4, 28 which led to funnel-plot asymmetry. Additionally, subgroup analyses for PFS were done basing on similar CTX, with evident decreased HRs for all of the subgroups; but significant heterogeneity was found in FOLFOX group (I 2 = 81.9%, q = 0.001).…”

“…33 Additionally, predictive markers in relation to the treatment effects with/without BEV were also explored, and the survival benefit with the addition of BEV in the treatment of mCRC is independent of the status of biomarkers, such as Kras, b-raf, and p-53. [26][27][28]34 But D-dimer may represent a useful biomarker for patients treated with antiangiogenic agents, though strongly correlated with OS, but not PFS. 23 In conclusion, BEV, acting as a targeted and antiangiogenic cancer therapeutic agent, is of efficacy and feasibility in adjuvant to CTX.…”

XELOX Plus Bevacizumab vs. FOLFIRI Plus Bevacizumab Treatment for First-line Chemotherapy in Metastatic Colon Cancer: a Retrospective Study of the Anatolian Society of Medical Oncology

“…Addition of bevacizumab to XELOX resulted in PFS ranging between 9.3-11.4 mo, OS ranging between 20.3-27.4 mo and a RR ranging between 46%-67.5% (Hochster et al, 2008;Tol et al, 2009;Doi et al, 2010;Cassidy et al, 2011;Uchima et al, 2014). Previous studies reported that the median PFS was between 9-12 months and the median OS was between 22-31.3 months and RR was 57.9% with FOLFIRI-Bev (Fuchs et al, 2007;Hecht et al, 2009;Sobrero et al, 2009;Stathopoulos et al, 2010;Ducreux et al, 2013;Becouarn et al, 2014). In our study, the median PFS was 9.6 months in Group 1 and 9 months in Group 2 (p=0.019).…”

“…In different studies, investigators reported various partial response rates such as 47.5 (Becouarn et al, 2014), 40.1% (Pectasides et al, 2012) and 36.8% (Stathopoulos et al, 2010) with FOLFIRI-Bev. Lopez et al, reported a 8.4% complete response, 42.1% partial response, 16.8% stable disease and 32.6% progressive disease with FOLFIRI-Bev (Lopez et al, 2010).…”