Biosimilar Bevacizumab in Patients with Non-Small Cell Lung Cancer

Biosimilars and Generics

The chemical structure of the drug in a biosimilar product does not have to exactly match the original, making the path of biosimilars to market more complicated than that of traditional generics. Unlike generic chemical drugs, where demonstrating comparable pharmacokinetic properties is sufficient, biosimilars always require clinical studies to prove safety and efficacy comparable to the original product. The STELLA clinical evaluation compared the original bevacizumab with the biosimilar molecule MB02 in patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

STELLA Clinical Study – Course and Objectives

In the randomized double-blind phase III study, participants underwent a total of 6 cycles of treatment with either the original or biosimilar bevacizumab, each combined with chemotherapy (paclitaxel + carboplatin) every 3 weeks. This was followed by monotherapy with the original or biosimilar bevacizumab until disease progression, uncontrollable toxicity, treatment termination, patient death, or the scheduled end of study participation in week 52.

Independent radiologists assessed the objective treatment response in week 18, i.e., after the conclusion of chemotherapy. Progression-free survival (PFS) and overall survival (OS) of the patients were also monitored.

Comparison Results

A total of 627 patients with newly diagnosed or recurrent NSCLC participated in the study. The objective response rate (ORR) in week 18 was comparable in both arms (40.3% for MB02 vs. 44.6% for the original bevacizumab). The relative risk (RR) was 0.910 (95% confidence interval [CI] 0.758–1.092) and the risk difference (RD) was -4.02 (95% CI -11.76 to 3.71), falling within predefined bounds, leading the authors to consider both molecules as comparably effective. Both arms showed no significant differences in PFS and OS at the end of the study. Patients treated with MB02 had a median PFS of 36.0 weeks compared to 37.3 weeks for the original bevacizumab (hazard ratio [HR] 1.187; 95% CI 0.98–1.44). Median OS was not reached in either arm by the end of the study (HR 1.108; 95% CI 0.83–1.49).

The efficacy results were also supported by sensitivity analyses. The authors demonstrated that missing data and handling it through the multiple imputation method did not significantly bias the results in any direction.

In terms of safety, both drugs were also comparable. The RD for the occurrence of adverse events related to the administered drug did not differ by more than 5% between the two arms. There were no observed differences in the intensity and nature of adverse events. Both arms showed comparable occurrences of adverse reactions involving blockade of the vascular endothelial growth factor (VEGF), such as gastrointestinal perforations and fistulas, hypertension, proteinuria, thromboembolic complications, or bleeding.

Conclusion

Patients with NSCLC from the STELLA clinical evaluation who were treated with the biosimilar bevacizumab MB02 achieved comparable clinical results to patients treated with the original bevacizumab. In terms of efficacy and safety, the MB02 molecule was clinically equivalent to the original molecule.

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Sources:

1. Trukhin D., Poddubskaya E., Zoran A. et al. Efficacy, safety and immunogenicity of MB02 (bevacizumab biosimilar) versus reference bevacizumab in advanced non-small cell lung cancer: a randomized, double-blind, phase III study (STELLA). BioDrugs 2021; 35 (4): 429–444, doi: 10.1007/s40259-021-00483-w.
2. Trukhin D., Poddubskaya E., Zoran A. et al. Bevacizumab biosimilar (MB02) and reference bevacizumab in patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC) (STELLA study): multiple imputation analysis. J Clin Oncol 2021; 39 (15_suppl.): e15003, doi: 10.1200/JCO.2021.39.15_suppl.e15003.
3. Generics and Biosimilars Initiative. Biosimilars of bevacizumab. GaBI Online, 2021 Feb 5. Available at: https://gabionline.net/biosimilars/general/Biosimilars-of-bevacizumab