Background: It is crucial that the safety profiles of biosimilars are similar to those of the original biologics. A better understanding of biosimilars and their relative safety and immunogenicity profiles are required for healthcare providers to prescribe them to patients with life-threatening cancer diseases who receive chemotherapies with potentially serious adverse events (AEs).
Objectives: The purpose of this study was to collate and analyze currently available safety and immunogenicity outcomes of biosimilars used in oncology and compare their safety information with those of the original biologics.
Methods: The MEDLINE and Cochrane Library databases were searched as at 28 February 2022. Four anti-cancer biosimilar molecules were considered: bevacizumab, trastuzumab, rituximab, and (peg)filgrastim. Through a systematic review, we selected the randomized controlled trials (RCTs) comparing safety outcomes between the biosimilars and original biologics of the four molecules. As safety outcomes, various treatment-emergent adverse events (TEAEs) were collated, such as any TEAE, serious AE, and TEAE higher than grade 3. A risk ratio (RR) per category of TEAE was estimated through a meta-analysis. A network meta-analysis (NMA) was also conducted to compare the safety among the biosimilar brands for TEAEs over 25% with higher variability in addition to the serious AE cases.
Results: Forty-nine RCTs were identified. The results from the meta-analysis showed that the safety and immunogenicity profiles of all four biosimilar molecules are comparable with that of the original biologics at the TEAE level without statistically significant differences, except for diarrhea for (peg)filgrastim. The incidence of diarrhea with (peg)filgrastim was less than that with the original biologic (RR 0.66, 95% confidence interval 0.50-0.89). The NMA results showed similar safety profiles among the biosimilar brands for all four biosimilar molecules, except for the serious adverse event of a trastuzumab biosimilar (RR 0.296, 95% credible interval 0.109-0.840).
Conclusion: The meta-analysis and NMA for all four biosimilars showed that the safety and immunogenicity profiles of biosimilar products in oncology are generally comparable with that of the original biologics at the TEAE level. However, additional evidence needs to be collected since several TEAEs of specific biosimilars were out of the equivalent range. The results of this study provide comparative safety information and a better understanding of oncology biosimilars for healthcare providers to prescribe them to patients.
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.