Bevacizumab Biosimilars Show Similar Efficacy, Safety in NSCLC

Patients with non-small cell lung cancer (NSCLC) taking bevacizumab biosimilars demonstrated equivalent therapeutic efficacy and similar safety profiles to those taking the originator product, Avastin. | Image Credit: Ekaterina - stock.adobe.com

Bevacizumab biosimilars show equivalent therapeutic efficacy and similar safety profiles to the originator products when managing locally advanced or metastatic non-small cell lung cancer (NSCLC), according to a study published in Frontiers of Oncology.¹

The FDA has approved 5 bevacizumab biosimilars that reference Avastin (bevacizumab). Amgen’s Mvasi (bevacizumab-awwb) received approval in September 2017, followed by the approval of Zirabev (bevacizumab-bvzr; Pfizer) in June 2019.²

In 2022, both Alymsys (bevacizumab-maly; Amneal Pharmaceuticals) and Vegzelma (bevacizumab-adcd; Celltrion Healthcare) were FDA approved. Avzivi (bevacizumab-tnjn; Bio-Thera Solutions) was the most recent bevacizumab biosimilar to receive FDA approval in December 2023.

As lung cancer remains the leading cause of cancer-related death across the globe, innovative therapies are being utilized to target and address disease progression.¹ Combination therapies are gaining popularity, which could lead to biosimilars helping reduce health care spending without compromising therapeutic effectiveness. When a reference drug’s primary patents expire, biosimilars can foster market competition, reduce costs, and enhance patient access to vital biologic therapies.

The study authors compared the safety and effectiveness of bevacizumab biosimilars with the reference drug in combination with chemotherapy for NSCLC. They did this to examine the context of rising health care costs, enhance affordability, and broaden patient access to life-saving treatments.

Researchers conducted a retrospective analysis between January 2021 and December 2023 that enrolled 1058 patients who received 1 of the 5 versions of a bevacizumab biosimilar dosed at 15 mg/kg intravenously every 21 days (originator, n = 452; biosimilar, n = 606). The median age of the participants was 60.5 years, with 56.52% male and 43.48% female. The gender distribution in the groups did not have significant differences either.

Efficacy and Survival Analysis

None of the patients achieved a complete response (CR). The biosimilar group had an overall response rate (ORR) of 27.41% (95% CI, 24.1%-31%), with 180 patients who experienced partial response (PR) and 361 patients who experienced stable disease out of 606 patients.

The reference group had an ORR of 29.79% (95% CI, 26.5%-32%) and a disease-free rate of 87.3%. In the initial treatment group, 142 patients developed PR, and 250 patients developed stable disease. Study results showed consistency with the FDA, European Medicines Agency, and the Pharmaceuticals and Medical Devices Agency in Japan.

Researchers split patients into 2 groups based on survival status (deceased or surviving). Smoking history, performance status, stage at diagnosis, and comorbidities showed significant associations with survival status (P < .05). The study found no significant associations between survival status and age, sex, or treatment regimen (biosimilar vs reference drug).

Comparative Safety

The biosimilars significantly increased the risk of hypertension in patients older than 70 years of age who were treated with a high dose of the drug compared with the reference product (P < .05). Both groups did not have significant differences in the incidence of hypertension after the exclusion of patients with a history of hypertension and those who had been treated with a very high dose.

Adverse events (AEs) were experienced in 76.42% of patients with a total of 2306 instances observed in which 3 or more grade 3 AEs occurred. The biosimilar-treated groups and originator groups had similar frequencies of transient AEs, most of them being grade 1 or 2. The study found no statistically significant differences in the occurrence of grade 3 and 4 transient AEs between the 2 groups.

In the biosimilar group, the most common treatment-emergent adverse events (TEAEs) were fever (8.71%) and anemia (9.15%). The initial drug group had the highest prevalence of anemia at 15.33%. Patients experienced fatigue, pneumonia, leukopenia, neutropenia, thrombocytopenia, hypertension, bleeding, and thromboembolism as other TEAEs.

Limitations and Future Directions

The retrospective design of the study introduces potential biases and confounding factors, which complicate balancing patient characteristics and treatment histories between the bevacizumab and biosimilar groups, the authors acknowledged. The various treatment protocols and dosages further clouded the isolation of individual drug effects. The absence of randomization potentially skewed outcomes and compromised the researchers' ability to compare the drugs.

Additionally, the brief follow-up periods limit the insights into long-term survival benefits. Researchers have not yet fully elucidated the study mechanisms, and other targeted treatments remain unexplored. The reported AEs lacked depth on the long-term impacts and quality of life considerations. The limited data on rare genetic mutation subgroups hinders robust conclusions on safety and efficacy, according to the study.

Addressing the study's limitations is crucial for advancing precision medicine and promoting equitable health care, as it can ensure the generalizability of treatment outcomes across diverse patient populations.

“Future research is essential to refine safety assessments, optimize patient benefit, minimize risks, and support evidence-based adoption of biosimilars in oncology,” study authors stated.

References

1. Zhang X, Chu X, Wang J, et al. Retrospective analysis of survival and safety of bevacizumab biosimilar and original drug combination chemotherapy in non-small cell lung cancer. Front Oncol. 2024;14. doi:10.3389/fonc.2024.1437762
2. Biosimilar approvals. The Center for Biosimilars^®. Updated February 24, 2025. Accessed February 25, 2025. https://www.centerforbiosimilars.com/biosimilar-approvals