Professor of Medicine
Director, Breast Cancer and Clinical Trials Education
Division of Hematology/Oncology
Department of Medicine
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California
Hope S. Rugo, MD, has disclosed that she has received funds for research support paid to her institution from Biotheranostics, Eisai, Genentech/Roche, GTx, Immunomedics, Incyte, Lilly, MacroGenics, Merck, Novartis, OBI Pharma, Pfizer, and Plexxikon.
In oncology, biosimilars were initially used only for supportive care (eg, filgrastim-sndz). In late 2017, however, 2 biosimilars gained FDA approval for the treatment of active cancers—bevacizumab-awwb and trastuzumab-dkst. Highlighted below are some key considerations for oncologists as we begin to prescribe biosimilars more frequently.
Adopting Biosimilars for Supportive Care vs Active Cancers
Many oncologists regard supportive care as an “easier to approve” area of biosimilar development, in part because suboptimal drug performance would have fewer ramifications in this setting.
For instance, even if a supportive care biosimilar were theoretically to perform less well than its originator, the clinical consequence of decelerated neutrophil recovery may be acceptable to oncologists. With less at stake, widespread acceptance accompanied the initial use of biosimilars for supportive care. This was appropriate, given that comparable efficacy to its originator was a criterion set and met for filgrastim-sndz. Now, with a few years of supportive care biosimilar experience behind us, no real concerns have emerged regarding efficacy, toxicity, or interactions.
By contrast, for active cancer therapeutics, where survival or cure are at stake, oncologists may set different standards to justify replacing an originator with its biosimilar.
Oncologists may also apply different standards when considering using a biosimilar in indications where it is combined with chemotherapy (where a striking improvement in survival is not expected) vs using a biosimilar indicated for breast cancer (where improvements in survival and pathologic CR rates are expected). However, it is important to understand that the studies conducted for approval of biosimilars have been large, have focused on the most sensitive clinical endpoints, and have shown comparable clinical efficacy to originator biologics. Thus, the questions facing oncologists may be less about efficacy and more about how to use biosimilars in clinical practice.
Extrapolation Among Oncologic Conditions
In switching from an originator to its biosimilar, clinicians certainly want to know that no differences in pharmacokinetics or drug interactions will derail treatment of their patients. A similar confidence is desired before taking a biosimilar studied in one setting and extrapolating its use to other settings, such as among different metastatic conditions or from a metastatic to a curable setting.
This is the crux of the issues facing providers. Based in part on historical data from their originators, with bevacizumab-awwb and trastuzumab-dkst, we can feel reassured that no unusual differences or interactions are expected in cases of such extrapolation.
For example, the trastuzumab originator has been combined with nearly every other agent available for the treatment of breast cancer. Except with anthracyclines, no safety issues or atypical interactions have arisen. Furthermore, combining biologic agents such as trastuzumab and pertuzumab has not been associated with any concerns regarding pharmacodynamic or pharmacokinetic interactions. Of most importance, the detailed analyses of both biosimilars support their use across different combinations, as in the treatment of various metastatic conditions.
In addition, a biosimilar contains the same amino acid backbone as its originator product. That fact, paired with the regulatory stipulation for equivalent (not better) efficacy, should mitigate any concern that a biosimilar would underperform when its use is extrapolated to other indications for which it is approved but unstudied.
As long as reasonable data exist—and they do—we should feel comfortable with extrapolation. The lack of efficacy, toxicity, or antidrug antibody concerns from comparative studies of biosimilars and their originators is quite convincing, and future small trials will further confirm our ability to use biosimilars across diseases and across different settings within a specific disease. Meanwhile, striking a balance between efficacy and cost means that undertaking large confirmatory studies in every single setting or disease is unreasonable, is unnecessary, and eliminates the very cost savings that make biosimilars such attractive options for treatment.
What has been your experience in prescribing biosimilars thus far? Share your insights in the comments box below or by participating in the polling question on the right. Then, tune in to the CME-certified video module that accompanies this commentary, wherein a multidisciplinary panel of expert faculty discusses the use of biosimilars across oncology, rheumatology, dermatology, and gastroenterology specialties.
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