Clinical trials evaluating biosimilars for cancer drugs appeared to be well-designed and showed results that were "statistically indistinguishable" from those of the original products, according to findings from a systematic review and meta-analysis.
The 31 cancer biosimilar studies of three reference drugs involved more patients than the original drug trials (mean number of patients 397 vs 302), were more likely to be randomized trials than single-group or observational studies (100% vs 50%), and were more likely to be double-blind rather than open-label (84% vs 17%), reported Aaron Kesselheim, MD, JD, MPH, of Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues.
"Our results do support patient and physician confidence in the efficacy and extent of testing of currently available biosimilars to treat cancer," they wrote in JAMA Oncology. "More widespread use of these products may help promote price-lowering competition."
Kesselheim and colleagues pointed out that while biologics are used by fewer than 2% of people in the U.S., they contribute to a significant share of prescription drug costs. Fostering competition with biosimilars has been expected to lower pricing and overall spending. However, once approved, biosimilars and the original products are not considered to be interchangeable, with some physicians remaining skeptical about their relative efficacy.
In this meta-analysis, the study authors assessed 31 biosimilar studies of bevacizumab (Avastin), trastuzumab (Herceptin), and rituximab (Rituxan) involving 12,310 patients compared with six original drug trials involving 1,811 patients.
The conclusions from this analysis "are reassuring to oncologists and their patients with lymphoma, breast cancer, and other cancers treated with these agents," wrote Douglas W. Blayney, MD, of Stanford University School of Medicine in California, and Samuel M. Silver, MD, PhD, of the University of Michigan Medical School in Ann Arbor, in an editorial accompanying the study.
"We should refine the methodology for future meta-analyses, continue patient-level observations to detect potential long-term differences among the agents and detect rare side effects that may emerge with wider biosimilar use," they continued. "Further investigations should be directed to reassure us that the biosimilar development program is delivering value."
Bevacizumab
Kesselheim and colleagues identified 11 studies comparing bevacizumab with a biosimilar. Six trials included patients with non-small cell lung cancer (NSCLC), while the other five included patients with metastatic colorectal cancer (CRC).
The analysis of the NSCLC studies, which all had a primary outcome of overall response rate (ORR), showed a summary risk ratio estimate of 1.02 (95% CI 0.94-1.10).
An analysis of three CRC studies with ORR as the primary outcome demonstrated a summary risk ratio estimate of 0.95 (95% CI 0.72-1.24), while two CRC studies with progression-free survival as the primary outcome showed a risk ratio estimate of 0.91 (95% CI 0.80-1.04).
Trastuzumab
Among five studies of patients with ERBB2-positive early breast cancer and four studies of those with ERBB2-positive metastatic breast cancer given trastuzumab or a biosimilar with a primary endpoint of ORR, there were no differences between the originator and the biosimilars, with summary risk ratio estimates of 1.08 (95% CI 0.95-1.24) for the early breast cancer studies, and 1.01 (95% CI 0.94-1.08) for the metastatic studies.
Rituximab
Ten studies evaluated the originator rituximab with a biosimilar -- seven for follicular lymphoma and three for diffuse large B-cell lymphoma. (A study on chronic lymphocytic leukemia was not included in the meta-analysis.) Again, no differences were found between the biosimilar and originator, with summary risk ratio estimates of 1.04 (95% CI 1.00-1.08) for follicular lymphoma and 1.01 (95% CI 0.96-1.05) for diffuse large B-cell lymphoma.
Kesselheim and colleagues noted that "[c]onducting large and expensive pivotal trials for biosimilar molecules that have already shown a high degree of similarity in pharmacokinetics and safety in smaller studies creates barriers to entry and reduces expected competition."
"The comparative size and rigor of the biosimilar trials in this study, particularly in light of the near-universal finding of noninferiority, thus raise important questions about how much testing should be required of biosimilars," they continued. "As the reliability and reproducibility of scientifically assessing biosimilars continue to develop, such similar outcomes will allow regulators to become more flexible with the extent of preapproval testing."
Disclosures
This study was supported by Arnold Ventures.
Kesselheim reported no disclosures. A co-author currently serves as a judicial clerk at the U.S. Court of Appeals for the District of Columbia Circuit. This article was written before his clerkship and represents only his personal views.
Blayney reported owning stock in Berkshire Hathaway, Madorra, and Artelo Biosciences, and relationships with BeyondSpring Pharma and Artelo. Silver reported personal fees from McGivney Global Advisors.
Primary Source
JAMA Oncology
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