Sandoz’ Edward Li on Using Filgrastim to Ease the Risk of Febrile Neutropenia

The Center for Biosimilars® (CfB): Hello, I'm Matthew Gavidia. Today, on the MJH Life Sciences® Medical World News, The Center for Biosimilars is pleased to welcome Edward Li, PharmD, a pharmacist and director of Health Economics and Outcomes Research for Sandoz. Great to have you on. Can you just introduce yourself and tell us a little bit about yourself?

Li: Sure. My name is Edward Li. I am an oncology pharmacist by training. And prior to my role here at Sandoz, I was in academia for about 15 years. And currently, I'm director of Health Economics and Outcomes Research, where I'm part of the strategy, design, and execution of health economics and outcomes research studies for Sandoz.

CfB: Zarxio [filgrastim-sndz] was approved 5 years ago as the first biosimilar in the United States. Can you say a few words about this and the impact that Zarxio has had on access to filgrastim?

Li: It has been 5 years and I'd like to point out that Sandoz was the first company to bring a biosimilar to US patients and have a biosimilar with documented saving to the health care system. So, this includes health systems, integrated delivery networks, payers, and patients. And the availability of biosimilar filgrastim generated about $1.2 billion in savings to the US health care system. In approximately 4 years—that’s 2016 to about the first quarter 2020—Zarxio was driving the majority of the market there.

As we continue to build on the real-world evidence of Zarxio, we noticed that health care systems are implementing biosimilars into their clinical practices at a growing rate. This is really encouraging for the future of biosimilars in the United States. Because as more biosimilars enter the US market, patients will be able to be treated with a biologic medicine and patient will have broader access to a broader set of more affordable treatment options.

CfB: Can you describe febrile neutropenia and the importance of filgrastim for patients receiving chemotherapy, especially for breast cancer?

Li: Patients receiving chemotherapy can experience a temporary reduction in their white blood cell counts because of that chemotherapy, and that's known as neutropenia. Febrile neutropenia occurs when that neutropenic patient also has a fever—that a temperature of greater than 100.3ºF—which can be a sign of infection. Now, febrile neutropenia is considered a medical emergency. Patients are immunocompromised and, if left untreated, infection can lead to sepsis. This can lead to more serious costly intervention, such as hospitalization and the use of intravenous [IV] antibiotics.

And especially during the COVID-19 [coronavirus disease 2019] pandemic, we want patients with cancer to avoid being hospitalized, where they can potentially be exposed to the coronavirus. So, febrile neutropenia can also lead to delays in chemotherapy administration, which may compromise the potential for these patients to achieve disease remission. Overall, febrile neutropenia after chemotherapy can lead to poor clinical outcomes and increased costs to the health care system.

CfB: What is the traditional setting for use of filgrastim in patients receiving treatment for breast cancer?

Li: A patient receiving chemotherapy for the treatment of breast cancer will be monitored for the development of febrile neutropenia. If needed, they'll receive an injection of white blood cell growth factors, such as Zarxio, at their infusion center and/or in their oncologist's office following their chemotherapy infusion. And the purpose of that is to prevent febrile neutropenia from occurring.

Now, when it comes to preventing febrile neutropenia after chemotherapy, there are 2 major strategies. The first is something called primary prophylaxis, where a growth factor, again, such as Zarxio, is administered directly following that first cycle of chemotherapy. The goal here is to prevent febrile neutropenia altogether. This strategy is usually reserved for regimens that are deemed to be at a high risk, as is the case with many breast cancer regimens.

The second approach is something called secondary prophylaxis, which can be seen as a watch-and-wait approach, whereby a growth factor is used only after a neutropenic event like febrile neutropenia is experienced after a prior cycle of chemotherapy. Now, this strategy is typically used for patients who are at a low or intermediate risk of developing chemotherapy-induced febrile neutropenia. Our study provides new information about primary prophylaxis in patients receiving intermediate risk chemotherapy, lower than what has traditionally been recommended, and answers the question about whether it's cost effective in these patients.

CfB: What has been the reason for doing it this way? You mentioned costs. Is it costs alone or is it moreso concern about adverse events from using filgrastim?

Li: Historically, due to the high cost of reference growth factors, patients who are at an intermediate risk are monitored for the development of febrile neutropenia before they would receive growth factors for subsequent cycles. And this is because the previous economic models demonstrated that it's cost effective for primary prophylaxis with a growth factor when patients are receiving high risk regimens. And this makes sense because with higher baseline febrile neutropenia risk, you'll avoid more hospitalizations and costly treatments with a primary prophylaxis strategy.

To our knowledge, ours is the first study demonstrating cost effectiveness using a growth factor of primary prophylaxis following intermediate risk chemotherapy and this was possible because of the reduction in price that was experienced with the introduction of Zarxio into the marketplace.

CfB: What is the theory behind use of filgrastim in earlier stages of treatment as primary prophylaxis for chemotherapy-induced febrile neutropenia, also known as FN?

Li: With primary prophylaxis, more episodes of febrile neutropenia are prevented compared to secondary prophylaxis, which is that watch-and-wait scenario. Because more febrile neutropenia events are prevented, you'll have fewer hospitalizations, use of IV antibiotics, and costs associated with these interventions as well. Further, patients are able to stay on time with their chemotherapy. This prevents delays in chemotherapy administration that could potentially compromise their chance of disease remission.

In addition, our world changed earlier this year, where we're now dealing with the coronavirus pandemic. Patients with cancer and especially those receiving chemotherapy have disproportionately worse outcomes if they contract the virus due to their compromised immune system. So, we want to reduce their potential exposure to the virus and support these patients' immune systems as much as possible.

Therefore, during this pandemic, the guideline-issuing bodies, such as the National Comprehensive Cancer Network and the American Society of Clinical Oncology, now recommend the administration of a growth factor as primary prophylaxis for febrile neutropenia in both the intermediate and high risk groups of patients following their first cycle of chemotherapy. And the goal here is to reduce emergency room and hospital visits.

So, our study supports and aligns with these updated recommendations. We have data showing that primary prophylaxis with Zarxio is also cost effective in these patients with lymphoma or lung cancer who are also receiving intermediate risk chemotherapy.

CfB: Can you tell us a bit about the risk for developing FN for patients receiving chemotherapy for breast cancer?

Li: The risk of developing febrile neutropenia will depend on a patient's individual chemotherapy regimen. And when patients with breast cancer receive chemotherapy for curative intent, they'll often be started on a high-risk regimen. One example of this is something called dose-dense doxorubicin cyclophosphamide.

Now, primary prophylaxis with a growth factor following this chemotherapy regimen is commonly used. Afterwards, patients may be transitioned over to an intermediate risk regimen. An example here would be a taxane, such as docetaxel, and a patient may receive that with or without anti-HER2 therapies, such as trastuzumab, depending on their HER2 status. And the use of growth factor as primary prophylaxis in this setting is less common.

In our study, we modeled patients who were on an intermediate risk regimen, specifically docetaxel, which is a taxane. It showed that Zarxio as primary prophylaxis is cost effective in the situation. It's important to note that no matter the regimen that they're receiving, all patients should be monitored for febrile neutropenia.

CfB: Can you tell us how you structured your study and the characteristics of the patients you enrolled?

Li: This study evaluates the cost effectiveness of Zarxio as primary prophylaxis in patients with early stage breast cancer who are receiving potentially curative chemotherapy that consists of docetaxel every 3 weeks for 4 cycles. And these patients are at an intermediate risk of developing febrile neutropenia. We developed a Markov model, which simulates, based on real world data, what would happen to a population of 56-year-old patients with early stage breast cancer over their lifetime if they received either the primary prophylaxis strategy or the secondary prophylaxis strategy after that intermediate risk chemotherapy. Again, that was adjuvant docetaxel. These patients completed their adjuvant doxorubicin cyclophosphamide therapy.

We also evaluated clinical outcomes in our study. These were febrile neutropenia events, life years saved and quality-adjusted life years, which is very similar to life years saved, but it incorporates a metric of being at good health. We also evaluated total costs, which included growth factor costs and hospitalizations for febrile neutropenia. Our study modeled that, with the primary prophylaxis strategy, this would result in better outcomes compared to secondary prophylaxis in terms of fewer febrile neutropenia events, increased life years saved, and increased quality-adjusted life years gained. And this was at an added cost but in the context of outcomes game, it's deemed to be cost effective.

CfB: Can you speak about your incremental cost savings and explain how they correlate to an advantage gained for use of biosimilar therapy in this setting?

Li: To answer this question, first, let me start with a rhetorical question. How much would you pay to gain 1 year of life at good health? In the United States, there's a common agreement that this is about $50,000. That means as a society, we're willing to pay about $50,000 per quality-adjusted life year gained.

Now, incrementally, the primary profile access strategy using Zarxio will cost more compared to secondary prophylaxis. But when you put that in context of what you gain, which is the quality-adjusted life years, it's about $35,000 per quality adjusted life year gained, and that's less than the $50,000 threshold that's deemed to be cost effective. And so, the point here is that with the introduction of biosimilars, the price was able to come down enough so that now, it's cost effective in this setting. If we were to do this analysis 10 years ago, when no biosimilars existed in the United States, it would not be cost effective.

CfB: Do you have any other further thoughts about the relevance of these findings and their significance for patient access and the reduction of unnecessary expense in the hospital or other settings?

Li: Our study demonstrates that it's cost effective to use a growth factor such as Zarxio, or primary prophylaxis in a wider population of patients than what's been traditionally recommended by guidelines in the past. And this supports the recent National Comprehensive Cancer Network recommendations in light of the COVID-19 pandemic, where it's now appropriate to use primary prophylaxis in intermediate risk patients, in addition to those at high risk. And the purpose of this is to improve clinical outcomes by reducing patient exposure to COVID, which [results in] disproportionately worse outcomes in patients with cancer.

Now, our breast cancer data builds on our evidence where we've demonstrated that primary prophylaxis with Zarxio is also cost effective for patients with non-small cell lung cancer or non-Hodgkin lymphoma receiving curative intermediate risk chemotherapy, and by demonstrating the cost effectiveness in a wider population of patients. We're delivering on the promise that biosimilars can increase access to historically expensive therapies, and logically it would follow that improved access will lead to better population-based outcomes.

CfB: To learn more, visit our websites at centerforbiosimilars.com. I'm Matthew Gavidia. Thanks for joining us.