DS-DS-8201 brings new hope for breast cancer

DS-DS-8201 brings new hope for breast cancer .  After breast cancer disease progresses, DS-DS-8201 brings new hope for treatment, but it can still bring new hope for treatment.

Breast cancer is already the world’s largest cancer, and medical scientists are also working hard to overcome it with research methods.

In 2020, breast cancer has become the number one cancer in the world. Among them, HER2-positive breast cancer accounts for about 20%. This type of breast cancer is highly invasive and has a poor prognosis.

At present, trastuzumab, pertuzumab, lapatinib, lenatinib and other drugs are mostly used for treatment, but there are still some patients who do not respond to HER2 targeted drugs or develop resistance after a period of treatment . What should we do at this time? Listen to what the breast cancer experts have to say.

▌HER2 positive or negative,  confused?

As everyone knows, HER2-positive breast cancer is the more dangerous type of breast cancer, but some sisters still don’t know whether their breast cancer is HER2-positive. Professor Cai Li from the Affiliated Tumor Hospital of Harbin Medical University gave a detailed answer to this question:

To determine whether you are a HER2-positive breast cancer patient, you first need to perform an immunohistochemical (IHC) test. If the IHC result is 0/1+, it means that the HER2 is negative and the HER2 protein is in a normal expression state; if it is 3+, then If it is HER2 positive, anti-HER2 treatment can be performed at this time; if it is 2+, it means that IHC alone cannot be determined, and in situ hybridization (ISH) is needed for further testing. If ISH shows positive, then you are suffering from HER2 Positive breast cancer; otherwise, it is not.

Among them, it is worth noting that if the HER2 test shows that the cancer in situ test 3+, it has no correlation with the significance of survival; if it is 3+ infiltration, it is what we call HER2-positive breast cancer, which requires anti- HER2 targeted therapy.

▌The HER2 nature of metastases can be either negative or positive

Most patients who are HER2-positive may have the recognition that if patients who are HER2-positive have metastases, their metastases must also be HER2-positive. Is this really the case? Let’s take a look at what Professor Du Caiwen from the Shenzhen Hospital of the Cancer Hospital of the Chinese Academy of Medical Sciences said:

In recent years, the survival rate of HER2 positive has increased, mainly due to the targeted therapy of HER2 gene, which reduces the recurrence rate of HER2-positive breast cancer and prolongs the survival period of patients with recurrence and metastasis. Therefore, for breast cancer patients, whether it is diagnosed, treated, or recurred or metastasized, it is particularly important to detect whether HER2 is positive.

Patients with HER2-positive breast cancer who have recurrence and metastasis need to be tested for HER2 again, especially the HER2 status of metastases. If re-puncture is performed on special parts such as the liver and brain, the risk is very high, so do not force it. Needle biopsy; while it occurs in soft tissues or on the body surface, we all support another biopsy of metastases.

▌Combined dual target combination, blocking cancer cell proliferation channel

For the sisters who had already determined that they were HER2-positive breast cancer and were treated with trastuzumab (Herceptin), they discovered that the disease had progressed after a period of treatment. Everyone can’t help asking, why does it relapse after treatment with Herceptin?

Let’s talk about the HER family again. The HER family has four members, namely HER1, HER2, HER3 and HER4. They can all promote the proliferation of cancer cells, while trastuzumab only inhibits HER2, the other three The HER members were not suppressed, all roads lead to Rome, one was blocked, and three were blocked. Therefore, it is understandable that there will be a relapse after using Herceptin.

Since one drug is not enough, there are two. It happens that Pertuzumab can complement the mechanism of Trastuzumab. The combination of the two can block all the pathways used and prevent cancer cells from making a comeback. In actual clinical trials, it has also confirmed the good effect of Tuotuo dual target. According to the six-year data of the APHINITY study, the risk of recurrence or death in the dual-target group was reduced by 24%.

▌Treatment options for HER2-positive breast cancer

Today, trastuzumab + pertuzumab + paclitaxel combination therapy has been the first-line recommendation for the first-line treatment of HER2-positive breast cancer patients. But if the house leaks in the night rain and the first-line treatment fails, then what treatment can be used for the second-line treatment? In response to this question, Professor Yin Yongmei of Jiangsu Provincial People’s Hospital answered:

According to the 2020CSCO breast cancer guidelines, for patients who have failed first-line treatment, that is, resistant to Herceptin, pyrrotinib + capecitabine is recommended for second-line treatment, and T-DM1 or Lapa is recommended for second-line treatment. Tinib + capecitabine;

For the second-line failure, the third-line and above treatments do not specify which drugs to use, so you can choose drugs that have not been used before. For example, if you have not used lapatinib in the first or second-line treatment, you can choose to use Lapatinib. Patinib: For patients with weak economic conditions, the use of T-DM1 and lapatinib will seriously increase the economic burden, so you can choose trastuzumab combined with chemotherapy for treatment.

▌DS-DS-8201 brings new hope for treatment

Breast cancer patients still have doubts about these treatments: The progression-free survival (PFS) and overall survival (OS) of patients with HER2-positive breast cancer in the third-line treatment are not high. Is there any way to improve it?

In the third-line and after the third-line treatment, the patient’s progression-free survival (PFS) and overall survival (OS) are indeed not high. Therefore, in the third-line treatment of HER2-positive breast cancer, we urgently need a method that can treat patients After the resistance of the first two-line treatments, drugs with good curative effects still appear. Finally, to live up to expectations, DS-8201 appeared!

DS-8201 is an antibody-drug conjugate (ADC) drug, consisting of trastuzumab + cytotoxic drug DXd + linker. It has a targeting effect and can accurately bring DXd to HER2 overexpressing tumors. In front of the cell, DXd can now enter the tumor cell body and play a role by virtue of its excellent “passing through walls” ability.

In addition to being able to accurately combat HER2 overexpressing tumor cells, DS-8201 can also exert a bystander killing effect, eliminating the “eat melon” tumor cells with low HER2 expression on the side.

▌Is DS-8201 really so amazing? Yes!

According to the results of the DESTINY-Breast01 study, the median PFS of DS-8201 reached 19.4 months, nearly 20 months in the treatment of breast cancer patients with a median of 6 lines, while the first-line treatment of trastuzumab + Pertuzumab The PFS of the monoclonal antibody is less than 20 months, only about one and a half years.

In addition, its objective response rate (ORR) is 61.4%. Of course, the further the front line, the higher the objective response rate. In general, no matter how many lines of systemic treatment the patient has received in the past, the ORR is more than 50%; the ORR of patients who have received only 2 lines of systemic treatment in the past has the highest ORR, reaching 76.7%.

Due to the outstanding performance of DS-8201, it was accelerated by the U.S. FDA in December 2019 for the treatment of advanced HER2-positive breast cancer patients who had previously received more than two anti-HER2 therapies. In January 2021, it was again approved by the European Commission for the previous use. Adult patients with unresectable or metastatic HER2-positive breast cancer who have received 2 or more anti-HER2 treatment regimens. I look forward to its approval in China and benefit more Chinese patients with HER2-positive breast cancer.

▌ADC drugs, you can use it if you want

Certainly some sisters were amazed by the efficacy of ADC drugs, so they couldn’t help but want to use ADC drugs as soon as the disease progressed, and wanted to experience them firsthand. Don’t worry, after reading Professor Sheng Yuan’s answer from Changhai Hospital Affiliated to Naval Military Medical University, it is not too late to make a decision.

The treatment of breast cancer is phased, which is reflected in the Ⅰ and Ⅱ recommendations in the guidelines. ADC drugs are currently mainly used for treatment after the second line. At present, we do not recommend that HER2-positive breast cancer patients progress as soon as the disease develops. Direct use of such drugs, but recommend that patients follow the doctor’s plan for treatment step by step.
Through the answers of the above-mentioned professors, we can see that anti-HER2 targeted drugs have brought significant therapeutic benefits to patients with HER2-positive breast cancer. The treatment options for HER2-positive breast cancer are also constantly diversifying. The advent of ADC drugs has enabled patients with HER2-positive breast cancer to be treated with drugs after their disease has progressed, bringing new hope to patients in treatment.

Currently approved breast cancer ADC drugs include T-DM1 and DS-8201. In addition, the FDA has granted fast track designation for another ADC drug, ARX788. In the future, we look forward to more ADC drugs appearing to bring greater benefits to breast cancer patients.

With the development of medicine, the once troublesome HER2-positive breast cancer has been treated in endlessly.

(source:internet, reference only)

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