Biosimilars in Oncology: Emerging Data for Treatment Options

Enrique Soto Pérez de Celis, MD


February 14, 2022

Dr Enrique Soto Pérez de Celis addresses common questions about the value and role of biosimilar drugs in the treatment of cancer.

Are the abbreviated approval pathways in Europe and the United States reasonable for showing that the efficacy and safety of biosimilars is therapeutically equivalent to the proprietary index agents?

I think that the biosimilar approval pathways used by the FDA, the European Medicines Agency (EMA), and other organizations make sense in general. The higher price of innovator biologics reflects the more complex and expensive approval process they undergo versus biosimilars. By cutting this down, you actually make it possible for biosimilars to be cheaper than the originators. The pathways employed by the EMA and the FDA, which are similar, focuses on the structure of the molecule. It would be useful to have more long-term data particularly for some indications, for example for trastuzumab which is used in a curative setting, but the process of showing molecular similarity appears to be reasonable based on the experience so far.

In oncology, have the biosimilars generally met the goal of reducing costs for highly effective but expensive biologics?

It is still difficult to answer that question. In my experience, biosimilar drugs can reduce costs by 10%-25% or higher depending on the region, relative to originator biologics in cost-effectiveness studies, but the uptake in many parts of the world has so far been insufficient to show this advantage. In the US, for example, some data project savings of $50-$100 billion if available biosimilars were used consistently, but these savings have not yet been realized. However, we have seen an impact of biosimilars in Mexico, particularly in the case of filgrastim and pegfilgrastim. Most of our patients could not afford these growth factors, so we had to use chemotherapy regimens with a low risk for bone marrow toxicity as a risk-reduction strategy. Biosimilars have changed our clinical practice, and this is true in many other parts of the world. If you reduce a very expensive drug by 25%, that is meaningful.

Across the originator biologics for which biosimilars are now available, including rituximab, trastuzumab, bevacizumab, and bone marrow stimulants, does it appear that equivalence is similar across target cancers?

There are not as many studies as you would like, but most studies comparing biosimilars to originator drugs are showing similar safety and outcomes. Most of these studies have employed a noninferiority design. In cases where the originator biologic has multiple indications, such as rituximab, which is used to treat lymphoma and rheumatoid arthritis, it appears that biosimilars offer the same degree of benefit regardless of clinical goal. So, I think most data suggest that biosimilars are an excellent alternative in most or all cases across indications. However, the role played by the originator and the biosimilar are important. For bevacizumab in lung cancer, we don't need a lot of long-term data; with shorter studies looking at progression-free survival (PFS), we can see if it's equivalent. But for other indications, in which a time horizon for survival is 5, 10, 15 years — like breast cancer, with trastuzumab, and other molecules in the future — we should be expecting these overall survival data and making sure that our patients are actually cured by the use of biosimilars, because those treatments, again, are curative and that is a completely different ballpark from when you are talking about prolonging PFS in metastatic disease. Studies of biosimilar trastuzumab do show similar rates of pathologic complete response, or overall response rate, although the benchmark for approval is not as strict as for originator drugs. Shorter-term evidence of comparable benefit is reasonable for bevacizumab biosimilars, but many clinicians would love to see a study that shows equivalent overall survival for a trastuzumab biosimilar, and this requires much longer follow-up.

When several biosimilars are available for an originator biologic, should all be considered reasonable substitutes or would you advise clinicians to favor those biosimilars with which they have already developed experience?

This is a tricky question, particularly in the US, where many clinicians do not yet have a lot of experience with biosimilars. I think that this question, although it is important for the clinician, will be decided by payers in many cases. In the US, this will come down to whether Medicare or a private insurer has made an analysis and decided to go with a specific biosimilar. At least, that is what happened with the public healthcare system in Mexico. But from the clinician's standpoint, it is always good to go with what you know even if these biosimilars have been tested in the same way. Greater uptake of biosimilars is needed so that clinicians have experience and can feel safe when prescribing a biosimilar. With more clinical experience among physicians, pharmacists, and other healthcare workers, there will be more data in the healthcare system to detect adverse events. There is a huge need for biosimilar marketing surveillance.

In cancer, where overall long-term survival is the gold standard for gauging relative benefits, are survival data for biosimilars expected?

These types of long-term data should not be required for approval. If the approval burden requires years of follow-up, it will leave no room for cost savings. However, I do think that we do need to see proof of the same overall survival benefits eventually. We also need data to rule out differences in long-term toxicities. If these biosimilars do not achieve similar outcomes in the long term once data are available, we should rethink their use. Again, the length of follow-up needed to confirm comparable benefit and safety is not the same across indications. For long-term survival in breast cancer, the time horizon might be 5, 10, or 15 years. For improvement in progression-free survival in the metastatic setting, similarity can be shown in a much shorter timeframe.



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