Randomised clinical endpoint studies for trastuzumab biosimilars: a systematic review

Area of Science:

• Oncology
• Pharmacology
• Regulatory Science

Background:

• Biosimilar uptake relies on clinician and patient confidence in marketing approval evidence.
• Trastuzumab biosimilars offer alternatives to the originator biologic, Herceptin.

Purpose of the Study:

• To evaluate the evidential role of randomized clinical endpoint studies in the marketing approval of trastuzumab biosimilars.
• To assess the quality of evidence supporting trastuzumab biosimilar approvals.

Main Methods:

• Systematic review of PubMed for published randomized studies of EMA-approved trastuzumab biosimilars.
• Searched ClinicalTrials.gov for ongoing or unpublished studies.
• Applied GRADE criteria to assess evidence quality.

Main Results:

• Identified seven published randomized clinical endpoint studies for five EMA-approved trastuzumab biosimilars.
• Classified isolated randomized studies as low-quality evidence due to surrogate endpoints and small sample sizes.
• Determined the totality of evidence for each biosimilar as high-quality, indicating no clinically important differences from Herceptin.

Conclusions:

• Pivotal data for marketing approval relied on in vitro analytic characterization, not randomized clinical endpoint studies.
• Regulatory confidence in in vitro data is based on extensive experience with originator biologics.
• This emphasis on in vitro characterization represents a shift in oncological evidence evaluation.