Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

This was originally published on The American Journal of Managed Care

The adalimumab biosimilar Idacio (adalimumab-aacf) will be available to beneficiaries of Blue Shield of California at a steep reduction over the price of the reference product (Humira), which treats patients with inflammatory diseases.1 The biosimilar will be purchased at a net price of $525 per monthly dose compared with the $2100 net market price for the originator.

Blue Shield of California will offer an adalimumab biosimilar at a price that is 75% less than the reference product Humira for the monthly dose. | Image credit: gopixa - stock.adobe.com

Over the past 2 decades, more than 300,000 Americans used adalimumab annually. Blue Shield of California reported processing an estimated 40,000 adalimumab prescriptions every year, making it necessary to find an alternative option that is affordable.

“We will no longer take part in a pharmacy system that is designed to maximize the profit of participants instead of the quality, convenience and cost-effectiveness for consumers,” Paul Markovich, CEO of Blue Shield of California, said in a statement.

Fresenius Kabi and Evio Pharmacy Solutions partnered with Blue Shield of California to facilitate cost reductions and were able to eliminate the price markups applied in traditional pharmacy benefit manager (PBM) models. Instead, Blue Shield of California asserts that its new Pharmacy Care Reimagined model will offer patients better access to biosimilars.

The collaboration between the 3 stakeholders led to agreements on aligned incentives and the removal of excess complexities that has allowed the adoption of lower-cost medications despite supply chain shortages. Nearly all patients with Blue Shield who take Fresenius Kabi’s adalimumab-aacf will pay $0 out of pocket, beginning January 1, 2025, which could help improve medication adherence.

Evio Pharmacy Solutions, a pharmacy solutions startup founded by the Blues, is directly purchasing Idacio from Fresenius Kabi in a model that is designed to minimize net costs and create transparency.2

The growing number of biosimilar drugs is increasing price transparency in the market. This is evident with the recent launch of several adalimumab biosimilars, including adalimumab-atto (Amjevita) in the US.3 Amgen, the manufacturer, applied a pricing strategy that offers discounts based on patient insurance coverage and has contributed to a steady decline in the market share of the original drug, Humira.

“Humira has drawn scrutiny for its high and inconsistent pricing from both consumers and policymakers,” said Matt Gibbs, vice president of pharmacy transformation at Blue Shield of California.1

The Biosimilars Council revealed in an analysis from this past year that both patients and health plans were missing out on billions of savings because of PBM rebate policies.4 The analysis found Humira was costing patients, employers, and health plans around $700 million in increased drug costs and fees for each month since the launch of the first biosimilar.

The Biosimilars Council is pushing for the FDA to streamline its regulatory procedures for biosimilars.5 They believe regulations are unnecessary when there are no clinical differences between a biosimilar and its reference product.

“The time is now to update and streamline the current regulatory model for biosimilars,” stated Craig Burton, executive director of the Biosimilars Council. “Around 80% of biologics currently do not have a biosimilar product in the works. Let’s reduce that percentage and pave the way for a new generation of lower-cost medications.”

Blue Shield of California slashes cost of world’s best-selling drug. Blue Shield of California. News release. October 1, 2024. Accessed October 2, 2024. 

https://news.blueshieldca.com/2024/10/01/blue-shield-of-california-slashes-cost-of-worlds-best-selling-drug

Evio announces groundbreaking direct purchase agreement for adalimumab biosimilar. Evio Pharmacy Solutions. News release. October 1, 2024. Accessed October 4, 2024. 

https://www.prnewswire.com/news-releases/evio-announces-groundbreaking-direct-purchase-agreement-for-adalimumab-biosimilar-302263346.html

Joszt L. Biosimilar competition erodes Humira’s market share; Amjevita leads the pack. 

. September 22, 2023. Accessed October 7, 2024. 

https://www.ajmc.com/view/biosimilar-competition-erodes-humira-s-market-share-amjevita-leads-the-pack

Jeremias S. Biosimilars Council: PBM rebate schemes cost Americans, payers $6 Billion. The Center for Biosimilars

. April 10, 2024. Accessed October 3, 2024. 

https://www.centerforbiosimilars.com/view/biosimilars-council-pbm-rebate-schemes-cost-americans-payers-6-billion

Jeremias S. Biosimilars Council position paper calls for end to clinical efficacy trials for biosimilars. The Center for Biosimilars. June 4, 2024. Accessed October 7, 2024. 

https://www.centerforbiosimilars.com/view/biosimilars-council-position-paper-calls-for-end-to-clinical-efficacy-trials-for-biosimilars

Articles

Blue Shield of California will offer an adalimumab biosimilar at a price that is 75% less than the reference product Humira for the monthly dose.

Blue Shield of California Lowers Humira Biosimilar Costs, Challenges PBM Pricing

Ivo Abraham, PhD, RN.

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center, recalls when he first began biosimilar research in the US in an interview with The Center for Biosimilars

Abraham emphasizes the current challenges that prevent greater biosimilar uptake and discusses techniques manufacturers can use to initiate more affordable drugs. He also mentions the doubts many expressed in the early years of biosimilar development.

This transcript has been lightly edited for clarity.

What are some of the challenges that biosimilar companies face when gaining market acceptance in the US? How have they been addressed?

We're going see more developments in terms of how biosimilars will be on the market. The detailing approach has not worked. The early days of biosimilars in the US, going from place to place trying to sell your biosimilar, that is too expensive; you cannot afford that.

There are some very interesting developments. For example, Cordavis, which is under CVS and a biosimilar company that they are aligned with. If you look at the Marc Cuban Cost Plus Drug pharmacy, they have certain agreements. Manufacturers of biosimilars need to continue getting volume contracts to stay active on the market.

To be honest, Gary [Lyman, MD, MPH, oncologist, hematologist, and public health researcher] and I took a big gamble in 2007; we had been doing work in biologics and growth factors internationally since 1998. The people that we've worked with at J&J [Johnson & Johnson], Roche, Amgen, and so on were then being recruited by the biosimilar manufacturers. Then they literally called us up and said, "Can you help us out?” I remember Gary and I were talking, thinking, this could be big.

I also know that some people said, "They must not be doing well since they're doing generics now." For us, it's really been the goal from the beginning to increase access, then we started formulating that more recently into equity, and that is what generics, biosimilars, and bioparallels are.

Videos

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center, discusses the potential of biosimilars and challenges in the US, emphasizing partnerships for market growth.

From Skepticism to Success: Insights Into Biosimilar Market Acceptance

Here are the top 5 biosimilar articles for the week of October 7, 2024. 

 of a mandatory nonmedical switch in Canada found no significant differences in rates of treatment persistence, loss of response, or adverse events in patients with inflammatory bowel disease (IBD) on maintenance therapy 1 year post-switch.

, the FDA approved a new biosimilar for treating retinal conditions, marking a significant development in the biosimilars landscape, coinciding with ongoing legal disputes in the industry and highlighting broader trends in market dynamics and regulatory challenges.

 a new strength of a trastuzumab biosimilar; UnitedHealth will remove reference adalimumab from some preferred drug lists in favor of biosimilars and Evernorth will offer an interchangeable ustekinumab biosimilar at no cost to patients; Samsung Bioepis received a positive regulatory opinion for its aflibercept biosimilar.

 these entrenched market dynamics, they must not only compete on price but actively work to build a network of support among providers and patients.

 was approved simultaneously in the European Union. In the US, it will launch in February 2025.

To read all of these articles and more, visit 

The Top 5 Biosimilar Articles for the Week of October 7

A study found that switching from rituximab to biosimilar CT-P10 is safe and effective for patients with systemic lupus erythematosus (SLE). | Image Credit: luchschenF - stock.adobe.com

Switching from originator rituximab to biosimilar rituximab (CT-P10) was found to be safe and effective in patients with systemic lupus erythematosus (SLE), according to a study published in the 

European Review for Medical and Pharmacological Sciences

SLE can be defined as an autoimmune disease where the body attacks healthy tissue, impacting the skin, joints, kidneys, brain, and other organs.

 Epidemiology of SLE is not quite clear but evidence suggests the condition is associated with genetics, environmental factors, hormones, and medications. Symptoms of SLE can vary widely, but often include joint pain, fatigue, skin rashes, and fever.

Treatment for SLE ranges but widespread evidence has found decreased B-cell counts result in positive effects through the induction of T cells that leads to the production of cytokines.

 The originator rituximab was developed to induce apoptosis of B cells by killing B cells mediated by complement and antibody dependent cellular cytotoxicity by antagonizing CD20.

Celltrion developed the first rituximab biosimilar, and it received approval in 2017 by the European Medicines Agency (EMA).

 The drug was originally made to treat non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, and granulomatosis with polyangiitis. This was the first biosimilar to receive market approval from the EMA and its usage approval is available for all indications of originator rituximab.

“The objective of our study was to analyze the efficacy and safety data of treatments with originator rituximab and CT-P10 molecules intra-comparatively,” the study authors stated.

Disease activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). SLEDAI-2K is a weighted scoring system that accounts for various clinical and laboratory factors associated with SLE to assess disease activity.

Most patients were female (86.4%), and they had a mean (SD) age of 40.3 (10.6) years. Treatment duration was 35.6 (23.0) months for the originator and 17 months for CT-P10. More than half of the patient population had at least 1 comorbidity present (68.2%), the most common being hypertension (63.6%).

The kidney was considered the most frequently involved organ (63.6%), and ischemic cerebrovascular accident was the most common neurological involvement pattern (22.7%).

SLEDAI-2K scores were 2 and 0, respectively, approximately 3 months before and after the administration of the first dose of biosimilar CT-P10. The SLEDAI-2K scores of the rituximab biosimilar represented a statistically significant difference (

 = .027). Three months after the first dose of CT-P10, the SLEDAI-2K score was significantly lower. The analysis identified differences between the SLEDAI-2K score 3 months after the last dose of the originator (median, 2.5) and the score found in patients around 3 months after the first dose of the biosimilar (median, 0.0) (

The rituximab originator had an adverse effect frequency during administration of 15.3 per 100 patient-years. Urinary tract infections were of the most common infections contracted (7.7 per 100 patient-years).

During administration of the biosimilar, the adverse effect frequency was 39 per 100 patient-years. Pneumonia was the most common infection among patients, at 19.5 per 100 patient-years.

The limited number of participants and study design limited the results. The duration of follow-up after switching to the biosimilar was shorter than the originator. The study also did not include a control group, and most patients were not in flare during the efficacy evaluation. The COVID-19 pandemic coincided with the time interval of switching.

Ekin A, Mısırcı S, Coşkun BN, Yağız B, Dalkılıç E, Pehlivan Y. The retrospective evaluation of efficacy and safety data after switching from originator rituximab to biosimilar rituximab (CT-P10) in patients diagnosed with systemic lupus erythematosus: a single-center experience. 

. 2024;28(10):3513-3522. doi:10.26355/eurrev_202405_36286

Systemic lupus erythematosus. MedlinePlus Medical Encyclopedia. 2018. Accessed October 3, 2024. 

https://medlineplus.gov/ency/article/000435.htm

Biosimilar approvals. The Center for Biosimilars

. Updated March 22, 2024. Accessed October 3, 2024. 

https://www.centerforbiosimilars.com/biosimilar-approvals

A study found that switching from rituximab to biosimilar CT-P10 is safe and effective for patients with systemic lupus erythematosus (SLE).

Biosimilar Rituximab Safe, Effective for SLE After Switching

Here are the top 5 biosimilar articles for the week of September 30, 2024.

 written by Vibeke Strand, MD, clinical professor in division of immunology/rheumatology at Stanford University School of Medicine, gave an overview of patient-reported outcomes (PROs) in the VOLTAIRE-RA trial.

 diving into the Association for Accessible Medicines' (AAM) latest report discusses that while generics and biosimilars saved $445 billion in 2023, their potential is hindered by high patient costs, drug shortages, and ineffective policies, underscoring the need for reforms to fully realize their benefits.

approved Celltrion's ustekinumab biosimilar

 for chronic inflammatory diseases, Celltrion expanded access to Zymfentra (subcutaneous infliximab-dyyb) through partnerships with Cigna and Express Scripts, and the Association for Accessible Medicines held a policy briefing addressing barriers to biosimilar adoption.

: The Inflation Reduction Act (IRA) has modestly boosted 

 through Medicare reimbursement, but its impact has been limited due to preexisting competitive market conditions.

The Top 5 Biosimilar Articles for the Week of September 30

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center, discusses the evolvement of the biosimilar landscape throughout the years in an interview with The Center for Biosimilars®.


Abraham addresses both biosimilars and generics, highlighting their potential to provide more access to patients at lower costs while recognizing the challenges of marketing biosimilars and the need for volume contracts to stay competitive.

This transcript was lightly edited for clarity.

The biosimilar landscape is constantly evolving. What emerging trends in health economics or clinical research do you see impacting the future of biosimilar development and access?

Price erosion is one because it can only go so low. We need to make sure that this does not threaten the biosimilar manufacturing side of the formulary. They have more costs to recover, so there needs to be some way, and it's probably going be more of a coordinated way of limiting the price erosion that we see for the reference products. We know a lot of those costs have already been recouped, whereas a biosimilar company still has to do that. Also, we are seeing the high volume agents that the manufacturer or the reference product is willing to go very, very low in terms of their price because it's made up in part by volume. That's an important aspect.

The other aspect that we need to take into account is we're not going to have influence over which biosimilar you're administered. It's the same thing as with a generic. You can go to the pharmacy and receive a 3-month supply from one company, and 3 months later, it may be another company just because your payer has different contracts or your pharmacy provider.

Dealing with the fact that we're talking about commodity markets, and as we've seen shortages in generic cancer drugs, for instance, manufacturers of generics are pulling out of producing certain treatments because of the margin being so minimal. This is not treating hypertensive patients, where you have millions and millions and millions. Just in the US, you may be talking about a much smaller patient population.

Another thing that is important is that, in the US, we need to let go of our xenophobism, that things that come from abroad are not good. When we talk about biosimilars, we're going to have to take into account that we have now entered also an era of bioparallels. These are products developed somewhere else, are of very high quality, very well researched, with clinical trials and so on, and will enter the US market or are entering the US market at a significant price discount relative to other very well-established products—and I'm referring to PD1 inhibitors—and will provide more access to more patients at potentially lower cost.

What we also need to take into account is that especially the manufacturers of biosimilars that also manufacture generics bundle their products. For instance, have a bundle of chemotherapy agents, not biologic agents, but chemotherapy agents with then a biosimilar of a biological product.

For instance, the first line of breast cancer treatment is highly myelotoxic. Patients are at very high risk of developing neutropenia or febrile neutropenia. Why not, as a manufacturer of generics and biosimilars, create a breast cancer bundle of products? Then the products could be priced accordingly and be sold to payers, providers, and patients.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, explains how biosimilars are becoming more accessible but face challenges like price erosion and potential shortages.

Future Biosimilar Trends, Challenges, and Opportunities

Here are the top 5 biosimilar articles for the week of September 23, 2024. 

 assessing patient satisfaction with adalimumab for inflammatory bowel disease (IBD) reported a high level of satisfaction with all adalimumab product, including biosimilars.

 with chemotherapy was effective in treating HER2-positive breast cancer, offering high safety and affordability.

: The article by Sarfaraz K. Niazi, PhD, critiques the irrationality surrounding biosimilars, suggesting that 

 in manufacturing could make biosimilars as affordable as generic drugs.

: Savings from generic and biosimilar drugs totaled $445 billion in 2023, showing promise for the growth of both markets and highlighting the success of expansion policies for these products, according to a new report from the 

: Amgen’s Pavblu (aflibercept-ayyh) is the 

 referencing Eylea (aflibercept) to be approved for American patients with retinal diseases.

Here are the top 5 biosimilar articles for the week of September 23, 2024.

The Top 5 Biosimilar Articles for the Week of September 23

Ivo Abraham, PhD, RN. 

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center, highlights the challenges and opportunities of biosimilar development and utilization in an interview with The Center for Biosimilars

Abraham suggests innovative risk-sharing models between manufacturers, payers, and providers to incentivize biosimilar development and ensure efficient utilization.

How can innovative risk-sharing models between manufacturers, payers, and providers incentivize biosimilar development and ensure efficient utilization once available?

We first need to ask ourselves, what are the risks of biosimilars? There is always a possibility that there are some extreme cases of a few patients where a biosimilar does not produce the clinical and safety aspects and it can be attributed purely to the biosimilar. So, if a patient has an adverse event or becomes febrile, neutropenic, then we can say it was not because the patients failed to respond to the treatment, that it was something related to the biosimilar. That probability is going to be very, very small, and it's minimal. We have modelled that statistically.

Now, there's the other part of the risk sharing that is important, and that is the financial risks. Their payers and biosimilar manufacturers need to cooperate, and probably need to cooperate on a little bit different model or approach that payers typically cooperate with manufacturers—that is, basically trying to get the lowest price.

We need to take into account that the manufacturer of the reference product is making proportionately a lot more money than the biosimilar company and has the latitude to also come down in price. We can term that 

 but think of it as competing in an increasingly commoditized markets.

The manufacturer of the reference products, we can ask why is it that they make more money proportionately, and it is because they don't have to recoup development costs, regulatory approval costs, legal costs, and so on and so on.

The manufacturer of the reference product to stay competitive has to also lower its price, come in at a lower price, and then either stay the same or minimally increase, but basically, it's a downsloping curve. In terms of the risk sharing, there is clinical risk, which is minimal, but the financial risk is a lot higher for biosimilar companies.

It took many of us by surprise, when suddenly, we saw the announcements—well some of us knew that there was something in the works—of what 

. They're saying they have an interest in using biosimilars as much as possible as a payer, so if they can also cut out more of the middle people, they can help some biosimilar manufacturers, work with them and help them with their developments and then have some kind of an agreement and then that becomes our biologic. Perhaps, this could even lead to the development of a new version of a particular biologic.

In the risk sharing, we see a lot more happening inside the house of the payer, as opposed to everybody sitting around the table and speaking on how to handle risk sharing. The risk is financial as opposed to in other treatment areas or newer treatment areas, where the risk is also clinical—for instance, a new monoclonal antibody that gets approved.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, analyzes the need for innovative risk-sharing models to promote biosimilar development and utilization.

The Role of Risk-Sharing Models in Biosimilar Adoption

Here are the top 5 biosimilar articles for the week of September 16, 2024.

 (aflibercept).1 The new product is approved for the treatment of retinal conditions, including neovascular age-related macular degeneration (wet AMD), macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy.

 Switching children with juvenile idiopathic arthritis (JIA) from anti–tumor necrosis factor originators to biosimilars showed 

similar disease activity and drug persistence

, with good tolerability, supporting the safety and effectiveness of non-medical switching.

 a 9% revenue increase in the first half of 2024, with over €2 billion in sales, driven in part by biosimilar successes and new product launches.

A study found patients with neovascular age-related macular degeneration (nAMD) 

 from aflibercept to the biosimilar ranibizumab, despite fluid challenges.

 While biosimilars could potentially lower costs and improve access to gene therapies, 

 in regulation, manufacturing, intellectual property, and market size pose challenges to their development and market entry.

Here are the top 5 biosimilar articles for the week of September 16, 2024. 

The Top 5 Biosimilar Articles for the Week of September 16

The combination of trastuzumab biosimilar and pertuzumab with chemotherapy was effective in treating HER2-positive breast cancer, offering high safety and affordability.

Trastuzumab biosimilar (Zercepac) and pertuzumab (Perjeta) combined with chemotherapy regimens showed efficacy among patients with HER2-positive 

HER2-positive breast cancer accounts for about 15% to 25% of all molecular subtypes. Common forms of neoadjuvant therapy for this cancer include targeted medications combined with chemotherapy, whereas adjuvant therapies are often forms of surgery.

The European Medicines Agency (EMA) approved the trastuzumab biosimilar in 2020 after a series of comparative quality, preclinical, and clinical studies confirmed its similar efficacy and safety to the reference product.

The trastuzumab biosimilar is administered through an intravenous drip into a vein for over 90 minutes either once a week or once every 3 weeks for patients with breast cancer.

 Typically, patients endure treatment for a year or until the disease returns. However, treatment for metastatic breast cancer continues for as long as necessary.

The EMA approved pertuzumab for combination use with trastuzumab and docetaxel for adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer in 2013.

Pertuzumab is infused into the vein at a recommended first dose of 840 mg over 60 minutes, followed by a 420 mg dose every 3 weeks, with each dose administered over half an hour to 1 hour.

Researchers aimed to conduct a single-arm real-world study to evaluate the efficacy and safety of trastuzumab biosimilar and pertuzumab combined with other chemotherapy regimens for patients with HER2-positive early or locally advanced breast cancer.

 The primary endpoint was the total pathological complete response (CR), and secondary endpoints were breast pathological CR, objective response rate (ORR), and disease control rate (DCR).

Participants included 22 female patients with HER2-positive breast cancer who received neoadjuvant therapy with a trastuzumab biosimilar and pertuzumab combined with chemotherapy, followed by surgery after 4 to 8 cycles of treatment. Breast cancer was in the left breast of 14 patients and right breast of 8 patients.

Variations of surgery included modified radical surgery (n = 7), mastectomy with sentinel lymph node biopsy (n = 6), and breast-conserving surgery (n = 9). Pathological evaluations found 15 patients achieved CR while 7 patients reached PR; 3 patients displayed CR in the primary breast lesion but had residual tumor cells in lymph nodes.

The study cohort had a breast pathological CR of 81.8%, a total pathological CR of 68.2%, and a breast retention rate of 40.9%. The combination of trastuzumab biosimilar and pertuzumab was comparable to the originator trastuzumab drug (Herceptin) at a 440 mg dose.

The study had a 100% ORR and DCR, meaning all patients achieved these efficacy end points.Most patients received the TCbHP regimen, a combination of 75 mg/m2 docetaxel and 6 mg/mL/min of carboplatin.

 The other patients received the THP regimen (docetaxel, trastuzumab, and pertuzumab) or EC sequential THP (epirubicin and cyclophosphamide combined with THP).

The study was limited due to the small sample size. However, its findings indicate that trastuzumab biosimilar and pertuzumab targeted treatment is effective among patients with HER2-positive breast cancer and offers high safety at low costs. Further research is required to support these findings, which could support the utilization of trastuzumab biosimilar in clinical practice.

Bao YF, Yang JZ, Li XF, Zhu JJ. Real-world clinical study of trastuzumab biosimilar (Zercepac) and pertuzumab (Perjeta) in combination with chemotherapy for neoadjuvant treatment of HER-2-positive breast cancer. 

. 2024;47(7):3225-3228. doi:10.1016/j.asjsur.2024.03.063

Burstein HJ, Hayes DF, Vora SR. Patient education: treatment of early HER2-positive breast cancer (beyond the basics). UpToDate. October 12, 2022. Accessed September 16, 2024. 

https://www.uptodate.com/contents/treatment-of-early-her2-positive-breast-cancer-beyond-the-basics/print

Henlius and Accord Healthcare receive EMA approval for Zercepac, trastuzumab biosimilar. News release. Henlius. July 29, 2020. Accessed September 16, 2024. 

https://www.henlius.com/en/NewsDetails-2670-26.html#:~:text=The%20approval%20was%20based%20on

‌Zercepac. European Medicines Agency (EMA). July 28, 2020. Accessed September 16, 2024. 

https://www.ema.europa.eu/en/medicines/human/EPAR/zercepac#:~:text=It%20is%20given%20by%20infusion

Boix-Perales H, Borregaard J, Jensen KB, et al. The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. 

. 2014;19(7):766-773. doi:10.1634/theoncologist.2013-0348

‌Perjeta. European Medicines Agency. September 17, 2018. Accessed September 16, 2024. 

https://www.ema.europa.eu/en/medicines/human/EPAR/perjeta

Lv M, Guo H, Wang C, et al. Neoadjuvant docetaxel with or without carboplatin plus dual HER2 blockade for HER2-positive breast cancer: a retrospective multi-center Chinese study. 

. 2020;9(6):2079-2090. doi:10.21037/gs-20-791

‌EC chemotherapy. Breast Cancer Now. Accessed September 16, 2024. 

https://breastcancernow.org/about-breast-cancer/treatment/chemotherapy/chemotherapy-drugs/ec-chemotherapy/