Two independent real-world studies have provided compelling evidence that bevacizumab biosimilars deliver significant cost savings while maintaining equivalent clinical outcomes compared to the originator product in patients with metastatic colorectal cancer (mCRC), addressing longstanding questions about the economic and therapeutic value of these alternatives in oncology practice.
Canadian Study Demonstrates Substantial Cost Savings
A population-based retrospective cohort study conducted in Ontario, Canada, revealed that prescribing bevacizumab biosimilars Mvasi and Zirabev as first-line treatments for mCRC patients provided substantial cost savings with no differences in life years or quality-adjusted life years (QALYs) compared with the originator Avastin.
The economic evaluation matched 742 patients who received biosimilars with 2,945 patients who received the reference product in a 1:4 ratio. Among biosimilar recipients, 635 patients (86%) received Mvasi and 112 patients (15%) received Zirabev. The analysis demonstrated a one-year patient-level cost savings of $6,379 CAD (95% CI, $3,537-$9,417), with mean total costs of $84,162 for biosimilars compared to $90,541 for reference bevacizumab.
Importantly, mean life years and QALYs showed no significant differences between the biosimilar and originator groups. The incremental net monetary benefit was estimated at $6,331 (95% CI, 6,245-6,417), while incremental net health benefit reached 0.127 life years (95% CI, 0.125-0.128) at a willingness-to-pay threshold of $50,000 per life year gained.
The researchers found that biosimilars remained cost-effective across multiple willingness-to-pay thresholds, including $100,000, $150,000, and $200,000 per life year gained. Subgroup analyses by biosimilar product and two-year analyses showed consistent cost-effectiveness results.
Indian Real-World Evidence Supports Clinical Equivalence
A complementary real-world study from India analyzed 944 patients with mCRC treated between 2017 and 2022, comparing outcomes between bevacizumab biosimilars and the reference product. The retrospective analysis included patients who received chemotherapy and bevacizumab at a single hospital, with 810 patients (86%) treated with biosimilars and 132 patients (14%) receiving reference bevacizumab.
The biosimilars evaluated included Bevacirel (Reliance Life Sciences), Bryxta (Zydus Cadila), and Versavo (Dr. Reddy's Laboratories). After a median follow-up of 18 months, the study found no significant differences in clinical outcomes between groups.
In first-line therapy, median progression-free survival (mPFS) was 10 months for the originator versus 9.3 months for biosimilars, with no significant difference (P = 0.62). Median overall survival showed similar equivalence at 17.8 months for the originator and 18 months for biosimilars (P = 0.85).
Among patients receiving second-line therapy, the pattern of equivalence continued, with no significant differences in mPFS (5.5 vs 5.8 months; P = 0.97) or median overall survival (8.2 vs 8.6 months; P = 0.16) between reference product and biosimilars.
Safety Profile Remains Consistent
The Indian study also evaluated safety outcomes, finding that the incidence of bevacizumab-related complications, including hypertension, fistula, and stroke, showed no differences between groups. While more perforations occurred among patients treated with biosimilars, the authors noted this included tumor perforations, suggesting the difference may not represent a true safety signal.
Addressing Healthcare Sustainability Challenges
The Canadian researchers emphasized that their findings address growing concerns about the economic burden of cancer treatment, which is largely driven by the costs of biologic drugs such as bevacizumab. As a monoclonal antibody targeting vascular endothelial growth factor, bevacizumab represents a significant treatment expense in oncology care.
The authors noted that previous economic evaluations from several countries had suggested the bevacizumab reference product was not cost-effective for mCRC at list prices, making the demonstrated cost-effectiveness of biosimilars particularly significant for healthcare systems.
Policy Implications and Clinical Confidence
The Canadian study's authors stated that their results confirm the benefits and cost savings possible with bevacizumab biosimilars in mCRC and justify Ontario's policy mandating biosimilar use for treating this condition. They suggested the findings could inform future policy decisions across Canada and other regions regarding bevacizumab biosimilar funding.
The Indian investigators emphasized that their results would help build confidence in biosimilars among healthcare professionals, noting that real-world evidence comparing outcomes to the originator had previously been limited despite biosimilars becoming available after Avastin lost patent protection in India in 2016.
Both studies address a critical evidence gap, as approvals for Mvasi and Zirabev in mCRC were based on extrapolation from randomized controlled trials in non-small cell lung cancer, creating what researchers described as "a paucity of indication-specific randomized-controlled trial and real-world evidence" for bevacizumab biosimilars in first-line mCRC treatment.
