On December 1, 2017, there was good news for Trastuzumab-dkst, a biosimilar to trastuzumab, an anti-HER2-targeted agent in breast cancer treatment, which received marketing approval from the U.S. Food and Drug Administration (FDA) for ” The FDA approved Trastuzumab-dkst for all indications of the “original” trastuzumab, including treatment of HER2-positive breast cancer.
The launch of Trastuzumab-dkst will provide new options for more breast cancer patients who need anti-HER2 targeted therapy, especially those who are less well-off.
What are biosimilars? Trastuzumab is a biotechnologically produced monoclonal antibody that is biologically active, which is a biologic drug. The word “similar” is used in relation to the “original” drug, meaning that the indication, efficacy, and safety of the drug is similar to the original drug being compared.
If it’s “similar,” why not just use it? Because of the complexity of biologics, it is almost impossible to have a biosimilar that is exactly the same as the original biologic drug. Biosimilars based on the “original” drug usually have to be revalidated in clinical trials before they can be officially marketed.
Trastuzumab
What do foreign studies say about trastuzumab biosimilars for breast cancer?
Trastuzumab-dkst is the first biosimilar to trastuzumab to be approved for marketing by the FDA. In addition to this, other trastuzumab biosimilars have come to fruition, and several countries such as South Korea and India have related have drugs on the market.
Trastuzumab-dkst
The phase III clinical trial of Trastuzumab-dkst for breast cancer is credited with bringing it to the clinic. The modified study selected 458 HER2-positive metastatic breast cancer patients divided into two groups to receive Trastuzumab-dkst or trastuzumab on top of paclitaxel-based chemotherapy, respectively.
After six months of treatment, patients in the Trastuzumab-dkst group had an overall remission rate of 69.6% compared with 64% in the trastuzumab group, with similar efficacy. After 1 year of treatment with the two anti-HER2-targeting agents, patients had progression-free survival rates of 44.3% and 44.7%, respectively, and overall survival rates of 89.1% and 85.1%, with no significant differences.
For safety, the incidence of neutropenia was around 55% in both groups, and serious adverse events were similar. The results suggest that trastuzumab-dkst is similar to the “original” trastuzumab as a first-line treatment for HER2-positive advanced breast cancer, but the safety profile remains to be seen over time.
CT-P6
CT-P6 is also a trastuzumab biosimilar that has received a lot of attention.
The clinical study of CT-P6 enrolled 549 patients with operable HER2-positive breast cancer in 23 countries around the world, who were divided into two groups and treated with CT-P6 or trastuzumab, respectively, before surgery, along with chemotherapy.
Preoperative dosing that achieves complete pathologic remission has the promise of better survival for breast cancer patients. In this study, patients had comparable rates of pathologic complete remission with CT-P6 compared with trastuzumab treatment (46.8% and 50.4% ), which in layman’s terms means about the same ability to kill tumor cells. The incidence of serious adverse events was also similar (6% and 8%).
On the basis of this data, it can be assumed that CT-P6 and trastuzumab have equivalent efficacy and similar safety profiles in patients with HER2-positive early-stage breast cancer. The drug has been submitted to the US FDA for marketing, and subsequent approval can be followed up.
ABP 980
ABP 980 is also a biosimilar to trastuzumab.
A large study enrolled 725 patients with HER2-positive early-stage breast cancer on the anti-HER2-targeting drug ABP 980 or trastuzumab before and after surgery in combination with chemotherapy for a full year after surgery.
The final results found that ABP 980 was not less effective than trastuzumab, and in early 2018, the European Medicines Agency (EMA) issued a positive opinion supporting approval of ABP 980 for the treatment of HER2-positive metastatic breast cancer and early-stage breast cancer.
Other trastuzumab biosimilars
Patent protection for the trastuzumab originator is expiring in various regions, and several biosimilars have been launched abroad, including Hertraz in India (2013), Herzuma in South Korea (2014), and HERtiCAD in Russia (2017). in late 2017, Ontruzant passed EU approval, and in early 2018 announced the launch of the drug in the UK.
As more and more anti-HER2 biosimilars become available, breast cancer patients will have greater access to targeted therapies that reduce the risk of death and increase their hope for survival.
Can I afford to use a biosimilar?
Can I afford biosimilars is surely the most important question.
Biosimilars of trastuzumab are generally cheaper, but because of the high cost of development, the price is only about 20% lower from abroad. For Chinese patients, also imported, the price of foreign biosimilars is not a significant advantage over originator drugs. Moreover, now that trastuzumab has entered medical insurance, the price has dropped significantly, reducing the economic burden of breast cancer patients.
If foreign drugs are expensive, is there a domestic trastuzumab biosimilar?
In fact, the state supports the development of domestic biosimilars from a policy level.
In fact, the state supports the development of domestic biosimilars from a policy perspective. Previously, the Drug Review Center of the State Food and Drug Administration (CFDA) specifically issued a notice seeking comments on “clinical study design and review considerations for trastuzumab biosimilars for injection.
Related research information shows that HLX02 and GB221 have entered phase III clinical trials (CTR20160526, CTR20160389, CTR20171510), and it is expected that domestic biosimilars can achieve better therapeutic effects.
Biosimilars vs. originator drugs, how to take them?
As mentioned earlier, biosimilars need to be validated in clinical trials to be similar in efficacy and safety to the original drug before they can be approved for marketing. But when you look at it, there are some differences in the similarities:
- Efficacy
- Efficacy. Originals have a long R&D investment and research time, and a more mature post-marketing regulatory regime. The majority of clinical trial data for biosimilars are short-term results, and long-term efficacy remains to be seen, with a long way to go for post-marketing effectiveness monitoring.
- Safety.
- Safety. The safety performance of biosimilars is limited to the observation period of a large study, and longer-term safety data will need to be accumulated over time.
- Price.
- Price. The lower price of biosimilars is one of their advantages, but the high cost of manufacturing and R&D is difficult to absorb in the short term, and price reductions are uncertain. Typically, biosimilar prices can be about 20% lower than originator drugs.
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To summarize, trastuzumab biosimilars have been marketed in the US, India, South Korea, Russia, and many other countries. Several biosimilars have also entered clinical trials in China, and Chinese breast cancer patients are expected to have access to cheaper targeted drugs in the future.
In the face of the myriad of targeted drug options, patients should not just pursue a particular treatment, but should consult with a medical professional and choose the most appropriate option based on their condition, financial conditions, and other factors.