New drug for lung cancer: The disease control rate is as high as 92%

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New drug for lung cancer: The disease control rate is as high as 92%

New drug for lung cancer: The disease control rate is as high as 92%.

The disease control rate is as high as 92%. This new anti-cancer drug is expected to become a new choice for the treatment of lung cancer patients!

When it comes to the “anti-cancer drug” in the tumor world, who do you think of? Is it the PD-1/L1 inhibitor that is popular recently, or is it aspirin that has been repeatedly screened because of the discovery of new curative effects?

This article will introduce to you a “blockbuster” in the anti-cancer world : DS-8201 , a cancer that has swept across the four major cancers of the lung, breast, stomach and intestine with its own super strength, and will be directed to the front line of lung cancer in the near future. Antibody-drug conjugates (ADCs for short) that initiate the treatment shock .

(Source: Screenshot of the official website of Daiichi Sankyo)

“Anti-cancer drug” DS-8201: Disease control rate up to 92%

As we all know, lung cancer is the malignant tumor with the highest morbidity and mortality in China, and about 3% of non-small cell lung cancer patients have HER2 gene mutation [1,2] .

The first-line treatment standard is chemotherapy or immunotherapy , but the efficacy is not satisfactory. Only about 27% of patients have an objective response to immune checkpoint inhibitors, and most of the remaining patients have poor response and poor prognosis.

Brain metastases often occur . In addition, there are also studies showing that small molecule inhibitors targeting HER2 mutations have certain efficacy, such as afatinib, but specific experimental studies are still in progress.

Just when nothing could be done, DS-8201 instantly reversed the situation with its own power , allowing us to see the dawn of the future for patients with HER2 mutations!

In 2020, the drug research company conducted a Phase I clinical trial of DS-8201 in 60 patients with HER2 overexpressing or mutated cancer, including 18 patients with non-small cell lung cancer (11 patients with HER2 mutation and 7 patients with HER2 overexpression) Experimental research, the results show [3] :

The objective response rate of patients with non-small cell lung cancer can reach 55.6%
The objective response rate for 11 non-small cell lung cancer patients with HER2 mutations was as high as 72.7%
Equally effective even for EGFR-targeted drug-resistant patients

New drug for lung cancer: The disease control rate is as high as 92%
(Phase I study: tumor size after DS-8021 in HER2-mutant advanced NSCLC)

In the same year, DS-8201 was re-announced at the ASCO annual meeting for 42 patients with HER2 overexpressed or mutated advanced non-small cell lung cancer (most of whom had received platinum-containing chemotherapy and immunotherapy, and 45.2% of patients had brain metastases). ) clinical data on monotherapy [4] :

The objective remission rate can reach 61.9%
Disease control rate as high as 90.5%
Most of the patients’ tumors shrank to varying degrees

New drug for lung cancer: The disease control rate is as high as 92%
(Phase II study: Change in tumor size from baseline in HER2-mutant advanced NSCLC treated with DS-8021)

In the latest clinical trial of DS-8201 published in the top medical journal NEJM in 2021, the researchers recruited 91 patients with HER2-positive non-small cell lung cancer , most of whom (95%) had received Over platinum-based chemotherapy, more than half of the patients (66%) had previously received immunotherapy, that is , they received DS-8201 again for a median of 6.9 months in the event of disease progression after treatment , and the trial results were also encouraging. Shock [5] :

Objective response rate up to 55%
The disease control rate is as high as 92%

And after a median follow-up of 13.1 months, the researchers found that these patients had a progression-free survival of 8.2 months and a median overall survival of 17.8 months!

New drug for lung cancer: The disease control rate is as high as 92% (Different types of HER2 gene mutation respond to treatment)

Comparing the results of the above several clinical trials, we can clearly find that DS-8201 has brought a very good effect on disease control and remission in patients with HER2-mutated non-small cell lung cancer.

What is even more exciting is that the official website of Daiichi Sankyo announced not long ago that the Phase III clinical trial of DS-8201 for the treatment of HER2-positive non-small cell lung cancer has completed the enrollment of the first subject .

This trial directly benchmarks K Drug (pembrolizumab), designed to evaluate the difference in efficacy between DS-8201 as first-line therapy and K drug combined with pemetrexed + platinum-based chemotherapy drugs, that is, once this clinical trial is successful, DS-8201 It will likely be approved for first-line treatment of lung cancer, bringing new hope to the treatment of lung cancer patients!

Targeted blasting to kill cancer cells

Having said so much, then what is the sacredness of DS-8201 and how powerful it is? Everything has to start with its own anti-cancer mechanism, antibody-drug conjugates (ADC).

To put it simply, an antibody-drug conjugate (ADC) is an anti-cancer “sniper” with two guns in hand. One gun is loaded with antibodies that can specifically recognize cancer cells, and it has the targeting of antibody drugs. The chamber of the gun is full of highly toxic chemotherapeutic drugs “bullets”, which are extremely lethal.

The dual guns combined with fixed-point blasting kill cancer cells, and “killing cancer is invisible”, and the side effects on the human body are relatively small . It is a rising star in the anti-cancer field in recent years.

The DS-8201, which also “holds two guns”, is the “popular fried chicken” in the antibody-drug conjugate (ADC) field. There are mainly the following two “bullets” in the chamber :

Antibody that accurately identifies cancer cells with HER2 targets (trastuzumab)
Highly toxic chemotherapeutic drugs (topoisomerase I inhibitors)

Due to the built-in antibody that accurately recognizes the HER2 target, the bullet can accurately hit the cancer cells with high or even low expression of HER2.

At this time, the therapeutic drugs will directly invade the cancer cells, and the targeted blasting will kill the cancer cells and resolve the problem.

The toxic and side effects brought by systemic chemotherapy also improve the lethality of targeted drugs , which can be said to kill two birds with one stone.

(DS-8201 Design Structure Source: dsi.com)

All cancer types in one sweep

In addition to “showing great powers” in the field of lung cancer, DS-8201 has achieved admirable results in breast cancer, gastric cancer, and rectal cancer:

HER2-positive gastric cancer [6] : The objective response rate (ORR) was 51.3%, and the disease control rate (DCR) was 85.7%
HER2-positive breast cancer [7] : The objective response rate (ORR) was 60.9%, and the disease control rate (DCR) was 97.3%
HER2-positive colorectal cancer [8] : The objective response rate (ORR) was 45.3%, and the disease control rate (DCR) was 83.0%

And before this, DS-8201 has been approved by the US FDA and Japan for the clinical treatment of breast cancer and gastric cancer.

In addition, the DESTINY-PanTumor02 study design was announced at the 2021 ESMO Annual Meeting to evaluate the objective response rate of DS-8201 in patients with locally advanced, unresectable or metastatic tumors with HER2 mutations , including Specifically: 7 patient cohorts with urothelial or bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, or rare tumors, all of whom had at least one disease progression after systemic therapy, and Patients who have received prior HER2-targeted therapy are allowed.

In this way, we can find that DS-8201 has a lot of “ambition” in the layout of the whole cancer species, and this also makes us more convinced that the dawn of HER2 mutation patients is not far ahead, and we believe that as more and more With the advancement of multiple clinical trials, more patients will benefit from this “anti-cancer drug”, and it is expected that DS-8201 will be approved for the treatment of lung cancer as soon as possible, bringing more hope to patients with non-small cell lung cancer .

References:

[1]. Campbell JD, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nat Genet. 2016 Jun;48(6):607-16.

[2]. Li BT, et al. HER2 amplification and HER2 mutation are distinctmolecular targets in lung cancers. J Thorac Oncol. 2016 Mar; 11(3): 414–419.

[3].Astra,Daiichi’s Enhertu shows early promise in her2 lung cancer

[4]. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINYLung01. abs 9504

[5]. Li BT, Smit EF, Goto Y, et al. Trastuzumab Deruxtecan in HER2-Mutant Non–Small-Cell LungCancer [J]. New England Journal of Medicine, 2021.

[6].Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer

[7].Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer

[8]. Salvatore Siena, et al., Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial, Lancet Oncol. 2021 May 4 ;S1470-2045

Editor in charge: Mijian Popular Science

Cover image source: Draft Design

New drug for lung cancer: The disease control rate is as high as 92%

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