Schwartzberg Explains Biosimilar Use in Clinical Practice

When choosing a biosimilar for a patient, a lot goes into the equation, said Lee S. Schwartzberg, MD, FACP, chief medical director of West Cancer Center and chief of the Division of Hematology/Oncology at the University of Tennessee Health Science Center, both in Memphis.

The strength of the regulatory process behind the biosimilar counts, as does the quality and breadth of clinical trial data, as well as the reliability of the supply chain and patient consent. But it’s also important to understand how data can be extrapolated to support the use of a biosimilar in diverse settings, Schwartzberg said.

He discussed all of these issues in an overview of how biosimilars are incorporated into his Memphis practice. Overall, these agents have been a successful experience for providers and patients, but some thought and a little discrimination needs to go into their selection, he said.

Off-Label Uses of Biosimilars

“The regulatory definition from the FDA is that you do 1 clinical trial in a sensitive population, so you can pick up any difference whatsoever between the originator and the biosimilar. And if you get a result that shows equivalence, then you can extrapolate that into other settings in the same disease. But also, you can extrapolate that into any other approved indication for a particular drug,” he said.

An example is trastuzumab, which is approved in gastric cancer and gastroesophageal junction cancers that are HER2-positive.

“The label for the trastuzumab biosimilars allows it to be used in those settings, even though it, to my knowledge, it has not been tested extensively in gastric cancer. Most of the studies have been in HER2-positive metastatic or early stage breast cancer, because that’s the overwhelming group that has this HER2 alteration.”

This extrapolation concept is important also within breast cancer, Schwartzberg said. “If you’re using a biosimilar that was tested in the neoadjuvant and adjuvant setting, it can also be used in the metastatic setting. So, if we have a patient with metastatic HER2-positive breast cancer for whom trastuzumab is indicated, which is virtually all of them, I feel comfortable also extrapolating and using it in that setting as well.”

Schwartzberg believes that any biosimilar can be extrapolated to any other indication in the FDA label for a reference product. “Because there are a lack of data in areas where there’s not an approval and where there weren’t previous studies, I would be hesitant to take a biosimilar, just like I would be with the originator, and use it in a nonindication situation, or at least where there have not been studies to date.”

The Importance of Savings

Biosimilars are a valuable addition to the armamentarium, but their chief advantage is that they cost less than originator products, he said. Development of these products is made easier by the simplified regulatory pathway that applies to biosimilars. Clinical development, the most expensive part of drug development, is less heavily emphasized among requirements for biosimilar approval.

“It’s more about showing that the molecule is like the originator molecule. You don’t have to spend tens of millions, or hundreds of millions of dollars to test [the biosimilar candidate] in every population in a large group of patients,” Schwartzberg said.

Biosimilars reduce costs for patients and the healthcare system because they are typically priced at a substantial discount to the originator drug.

“In our United States healthcare system, we need cost reduction maneuvers [such as biosimilar development], because the cost of cancer care, the cost of healthcare in general, is out of sight and out of control. So, anything we can do to reduce the cost without reducing the value or the effectiveness of a drug is a real benefit for everyone in the system.”

Consider the Source

One thing that does require careful consideration on the part of physicians is the origin of the biosimilar, in terms of manufacturing, Schwartzberg said. Biosimilars are complex biologics that have to be manufactured under very tightly controlled conditions, with quality assurance.

“You can’t just set up a plant and do this,” he said. “This is in living cells. Plus, because they’re so complex they actually can vary over time by a factory that’s doing it maybe a little differently than another. Over time it changes. So, it requires a lot of attention. Therefore, you should always think about the company that’s making it, their experience in making biologicals in the past, and the supply.”

Schwartzberg noted how distressing drug supply problems can be and why it’s important to consider stability of the supply chain when choosing a biosimilar for a patient. “The last thing you want is to be prescribing a drug to a patient that’s working and then call the manufacturer for another supply, and they say, ‘The factory went down and we’re not going to have it next month.’ That’s a terrible thing for a patient. So, reliability, experience in manufacturing biologicals, and making sure the supply chain is good, as well as the price, which is very important, are all factors to consider when choosing a biosimilar.”

Schwartzberg said his clinical experience with biosimilars has been very favorable. “I’m confident in the companies that are bringing biosimilars to market. We make sure that they are reputable companies with lots of experience and that we’re not going to have any disruption in the supply chain. We make sure that the pricing is fair, and that there’s value to every member, every [stakeholder]. And our patients have been very comfortable accepting biosimilars.”

The Importance of Patient Consent

In his practice, he explained, patient consent is paramount for decisions to use a biosimilar. The consent form includes a review of potential adverse effects so the patient is aware of them. “Biologicals, and biologicals like trastuzumab, which is an antibody, occasionally cause infusion reactions or other reactions. Like every other drug, and certainly every other biological, there is a potential for toxicity and adverse effects, as well as the specific adverse effects.”

When it comes to switching from a reference biologic to a biosimilar, the practice will have the provider talk to the patient and explain why the biosimilar is being proposed. Patients are told, “We have another version of the drug you’re getting. It works just as well as the other one. It’s a biosimilar, and it’s highly similar in terms of its efficacy and its safety, but it will cost you less, it will cost us less, and we’d like to change you to that. Are you comfortable with that?” Most of the time, patients are comfortable with the switch, and they know they are on a new drug, and the informed consent means everybody is protected, Schwartzberg said.