Efficacy and safety of bevacizumab biosimilars in metastatic colorectal cancer: A pairwise and network meta-analysis.

Abstract

e15566 Background: Colorectal cancer (CRC) is a significant contributor to cancer-related mortality worldwide. Bevacizumab is an established VEGF inhibitor for the management of metastatic CRC in addition to doublet chemotherapy. The data pertaining to comparison of biosimilars is limited. Methods: A systematic search after protocol registration (CRD420251179090) was conducted across PubMed, Cochrane, Google Scholar, Clinicaltrials.gov to identify relevant published articles or conference abstracts of randomized studies. The primary outcomes were objective response rate (ORR) and incidence of grade 3 or higher adverse events (AEs). Secondary outcomes were overall survival (OS), progression-free survival (PFS). Data was pooled as odds ratios (ORs) for binary outcomes and hazard ratio (HR) for time-to event outcomes with 95% confidence intervals (CIs). A pairwise and network meta-analysis was performed. Pooled estimates were generated using the Mantel–Haenszel method with random-effects models in RevMan 5.4. Analyses were stratified by the type of doublet chemotherapy, Oxaliplatin-based (O) or Irinotecan-based (I) regimen, with heterogeneity assessed using I² statistics. A network meta-analysis using the Bayesian approach was performed using the gemtc package in R v4.5.2. Ranking of biosimilars was done using the Surface Under the Cumulative Ranking Curve (SUCRA) values, with reference bevacizumab as the control. Results: Data from a total of 7 randomized studies with 1428 patients was pooled and analyzed. The ORR of all biosimilars together was comparable to the reference molecule (OR 0.94 95%CI 0.73-1.21, I 2 = 0%) as well as between the two chemotherapy regimens (OR O: 0.91 95%CI 0.70-1.18, I 2 = 0% and I: 1.32 95%CI 0.51-3.43, I 2 = 26%). The incidence of Grade 3 or higher AEs was also comparable between all biosimilars together and reference bevacizumab and between the chemotherapy regimens (OR 0.99 95%CI 0.76-1.30, I 2 = 0%; O: 1.07 95%CI 0.79-1.44, I 2 = 0%, I: 0.74 95%CI 0.41-1.33, I 2 = 0%). Survival outcomes did not differ significantly between biosimilar and reference bevacizumab (OS: HR 0.93 95%CI 0.70-1.24, I 2 = 0%; PFS: HR 1.02 95%CI 0.80-1.30, I 2 = 0%). Indirect comparison of individual biosimilars demonstrated clinical equivalence to one another for both ORR as well as the incidence of grade 3 or higher AEs. For ORR, BE1040V ranked highest (0.78 95% Crl -0.56, 2.19; SUCRA: 83.01%) in terms of efficacy. For grade 3 or higher AEs, DRL_BZ ranked highest (-0.68 95% Crl -0.51,1.93; SUCRA: 84.6%) in terms of safety. Conclusions: This analysis highlights biosimilar molecules of bevacizumab to bear clinical comparability to the reference molecule with BE1040V and DRL_BZ proving most effective for ORR and grade 3 AEs respectively. These findings emphasize the use of bevacizumab biosimilars in patients with metastatic CRC, guiding discretion of individualized treatment decisions.