Savings With Biosimilar Filgrastim Unclear

A simulation analysis funded by Sandoz Inc is projecting cost savings or more than $40 million if their biosimilar filgrastim, known as filgrastim-sdnz (Zarxio), is used instead of the reference drug (Neupogen, Amgen) for the prevention and treatment of febrile neutropenia in breast cancer patients who are Medicare beneficiaries.

A poster of the new analysis was presented earlier this month during the San Antonio Breast Cancer Symposium (SABCS) 2018.

However, the authors of an unrelated “real-world” simulation study of the use of biosimilars for the same indication say that to date, cost savings have been “modest,” in part because of similar pricing.

This second study, from a private healthcare analytics group, was published online November 3 in JAMA Oncology.

In the first study, lead author Gary Puckrein, PhD, National Minority Quality Forum, Washington, DC, and colleagues carried out a simulation to estimate the potential out-of-pocket cost savings for Medicare patients with breast cancer who undergo treatment with filgrastim-sdnz instead of reference filgrastim.

The researchers also estimated potential savings to Medicare on payments for the administration of the same biosimilar rather than the reference drug for the treatment or prophylaxis of febrile neutropenia in beneficiaries with breast cancer.

The average out-of-pocket cost for patients and any reduction in Medicare payments per claim were then calculated for patients who received filgrastim-sdnz instead of brand-name filgrastim.

This was then extrapolated to simulate 1 million claims from 100,000 Medicare patients at an estimated 10 claims per patient.

The average cost savings per claim for each patient treated with filgrastim-sndz instead of reference filgrastim was $9.51, the researchers report.

Extrapolated to 100,000 beneficiaries — or 1 million claims — the simulation model estimated that Medicare beneficiaries would save approximately $9.6 million if they were treated with filgrastim-sndz. Medicare would see a reduction in payments of $32.9 million if the same strategy were adopted.

“It is important to understand that this is a simulation model, so further analyses of real-world patient cases are needed to more thoroughly understand the appropriate patients who should receive a filgrastim biosimilar, as well as dosing needs,” Carlos Sattler, MD, vice-president of clinical development and medical affairs at Sandoz, North America, told Medscape Medical News in an email.

“But the main message emanating from this study is that Medicare patients who were prescribed biosimilar filgrastim saved about $9.60 per claim relative to those who were prescribed reference filgrastim, and this underscores the potential value of biosimilars in saving money for patients,” he added.

More filgrastim-sndz is prescribed now in the United States than reference filgrastim, according to Sandoz.

In 2012, the total cost for treating hospitalizations for cancer-related neutropenia was $2.3 billion for adults in the United States.

More Modest

On the other hand, an investigation of the real-world safety and effectiveness of biosimilar filgrastim compared with the brand-name drug suggests that cost savings to commercially insured patients in the United States are modest.

In a retrospective observational study, Abiy Agiro, PhD, HealthCore Inc, Wilmington, Delaware, and colleagues analyzed 11,202 commercially insured adults who underwent chemotherapy and were treated with either reference filgrastim or one of two biosimilar agents — the Sandoz product, and tbo-tiligrastim (Granix, Teva) — over a period of almost 5 years.

“Patients were observed for 21 days postindex to assess filgrastim treatment cost (total and per day of use) and the incidence of FN [febrile neutropenia] and AEs [adverse events],” the researchers write.

Of this large group of patients, 13.7% were prescribed biosimilar filgrastim, they note. (The use of biosimilar filgrastim has risen steadily from 7% of filgrastim users in 2014 to 36% of users in the United States 2016.)

“Incidence rates of strict (neutropenia and fever) and broad (neutropenia or fever) definitions of FN were similar between the 2 groups,” the researchers indicate.

The cost differential between treating patients with either biosimilar compared to reference filgrastim was also not that dramatic; the mean cost of treating a single patient with any one of the three products was very similar.

Table. Treatment Costs for Biosimilar Filgrastim vs Reference Filgrastim

Biosimilar Filgrastim Tbo-Filgrastim (Granix, Teva) Filgrastim-sndz Reference Filgrastim
Mean cost per day of use $731.00 $765.00 $667.00 $748.00
Mean treatment cost per patient $2522 $2585.00 $2363.00 $2516.00

“The cost per day of use was 2.3% less for biosimilar filgrastim,” the researchers indicate. “[T]he mean total cost per patient and per day of use were 6.1% and 10.8% less for filgrastim-sndz (P = .07 and P < .001, respectively) and were marginally higher for tbo-filgrastim (2.7% and 2.3%, respectively),” they add.

Agiro and colleagues point out that savings associated with biosimilar versions of filgrastim have been modest because uptake of these agents has been slow and because current pricing for biosimilar drugs closely tracks that of the reference product.

Dutch Study Links Implants to Increased Breast-ALCL Risk

Breast implants are associated with an increased risk — albeit small — of anaplastic large-cell lymphoma (ALCL) in the breast, according to Dutch researchers.

The results of the study, led by Mintsje de Boer, MD, of Maastricht University Medical Centre in the Netherlands, were published in JAMA Oncology.

 The study was prompted, the team explained, by the fact that the number of women with breast implants who have been diagnosed with breast-ALCL since 2008 has increased, with several reports suggesting a link between breast implants and breast-ALCL.

The researchers, therefore, performed a case-controlled study to determine the relative and absolute risks of breast-ALCL in women with implants.

Using the population-based nationwide Dutch pathology registry, de Boer and colleagues were able to identify patients diagnosed with primary non-Hodgkin lymphoma in the breast between 1990 and 2016 and then retrieved their clinical data, including breast implant status.

Among the 43 patients with breast-ALCL (median age of 59), 32 had an ipsilateral breast implant (median age of 56) compared with only one patient among 146 women with other primary breast lymphomas, resulting in an OR of 421.8 (95% CI, 52.6-3385.2) for breast-ALCL associated with a breast implant.

The investigators also examined the connection between specific types of implants and breast-ALCL. Of the 28 patients with breast-ALCL with a known implant type, 23 (82%) had macrotextured implants, which was more than expected considering that less than half (45%) of implants sold in the Netherlands between 2010 and 2015 were macrotextured.

 When looking at the absolute risk for breast-ALCL associated with breast implants, the researchers determined that the estimated prevalence of 20- to 70-year-old women with a breast implant in 2015 was 3.3%, ranging from 2.3% for those ages 20 to 30, 4.0% for those ages 31 to 40, 4.2% for those 41 to 50, 3.6% for those 51 to 60, and 2.1% for those 61 to 70.

The cumulative risk of breast-ALCL in the general population increased with age, reaching about 0.35 per million at the age of 75. For women with implants, the cumulative risk increased from about 29 per million at age 50 to about 82 per million at age 70. De Boer and colleagues calculated that the number of women with implants needed to cause one breast-ALCL case before the age of 75 was 6,920.

“Our relative risk estimate of over 400, implying an attributable risk approaching 100%, is highly suggestive of a direct or indirect causal role of the breast implant-associated ALCL,” de Boer and colleagues wrote.

They also pointed out that their calculations concerning the absolute risk of breast-ALCL has multiple implications considering the relatively large number of women (3.3%) in the Netherlands having implants. These include the need for comprehensive counseling of women considering having breast implants for cosmetic or reconstructive surgery, alternative cosmetic/reconstruction procedures, and the establishment of a registry program for breast implants and their complications.

As for the study limitations, de Boer et al noted that retrospective data on the prevalence of breast implants were not available because of an absence of breast implant registration — which only began in the Netherlands in 2016 — and the lack of reliable and complete historical implant sales data.

“Therefore our absolute risks of breast-ALCL in implant carriers were based on extrapolated data. Even in this nationwide study, numbers were too small to allow definite conclusions on modifying factors, such as duration of implant exposure and implant types.”

In an accompanying commentary, Colleen M. McCarthy, MD, and Steven M. Horwitz, MD, both of Memorial Sloan Kettering Cancer Center in New York City, wrote that while de Boer and colleagues should be commended for their “rigorous approach” to defining the risk of breast-ALCL in patients with implants, the conclusions appear to “more confirmatory than new.”

For example, as noted in this article in MedPage Today, the FDA earlier this year affirmed a link between ALCL and breast implants, and suggested that women with implants should be regularly monitored for signs and symptoms of the disease.

De Boer et al “conclude that breast implants are associated with a strongly increased relative risk of breast-ALCL, yet the absolute risk of the disease presented here remains extremely low,” McCarthy and Horwitz wrote, pointing out that most women with implants newly diagnosed with ALCL are successfully treated with implant removal and capsulectomy alone.

“For a woman and her physician considering options for implant-based surgeries, differences in underlying beliefs and values among women will sway decision making in different directions. Thus, when considering options where there is uncertainty, it is particularly important that the process of decision-making be shared, because these decisions are highly dependent on individual patient preferences and assessment of risk.”