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

This article will introduce to you a "blockbuster" in the anti-cancer world: DS-8201, a drug that has eliminated the four major cancers of lung, breast, stomach and bowel cancer with its super strength, and will be released in the near future.

"Anti-cancer drug" DS-8201: Disease control rate as high as 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 standard of treatment is chemotherapy or immunotherapy, but the efficacy is poor

Brain metastases occur frequently

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

In 2020, Drug Research conducted a Phase I clinical trial of DS-8201 in 60 patients with HER2-overexpressing or mutated cancers, including 18 patients with non-small cell lung cancer (11 patients with HER2 mutations and 7 patients with HER2 overexpression).

• The objective response rate of non-small cell lung cancer patients can reach 55.

• The objective response rate of 11 patients with HER2-mutated non-small cell lung cancer was as high as 72.

• Efficient even in EGFR-targeted resistant patients

• The objective remission rate can reach 61.

  
  

• Disease control rate as high as 90.

  
  

• Tumors shrink to varying degrees in most patients

• Target response rate up to 55%

• Disease control rate as high as 92%

After a median follow-up of 13.

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

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

Targeted blasting kills cancer cells

Having said all that, what is the sanctity of DS-8201? How powerful is it? Everything must start with its own anti-cancer mechanism, namely Antibody-drug conjugates (ADCs)
.

Simply put, antibody-drug conjugates (ADCs) are a cancer-fighting "sniper" armed with two guns
.
One of the guns is loaded with antibodies that can specifically recognize cancer cells, and it has the targeting properties of antibody drugs
.
The chamber of the gun is full of highly toxic chemotherapy drug "bullets", which are extremely lethal
.

The combination of double guns and fixed-point blasting kills cancer cells, "killing cancer invisibly", and has relatively little side effects on the human body
.
It is a rising star in the field of anticancer in recent years
.

DS-8201 is also a "dual gun" and a "popular hot chicken" in the field of antibody drug conjugates (ADCs)
.
There are mainly two "bullets" in the chamber of the gun:

• Antibody that accurately recognizes cancer cells targeted by HER2 (trastuzumab)

• Highly toxic chemotherapeutic drugs (topoisomerase I inhibitors)

Because the built-in antibody of the bullet can accurately identify the target of HER2, the bullet can accurately hit cancer cells with high or even low expression of HER2
.

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

The toxic and side effects of systemic chemotherapy also increase the lethality of targeted drugs, which can be described as killing two birds with one stone
.

One scan for all cancer types

DS-8201 has achieved admirable results in breast cancer, gastric cancer, and rectal cancer in addition to its "experience" in the field of lung cancer:

• HER2-positive gastric cancer[6]: Objective response rate (ORR) was 51.
  3% and disease control rate (DCR) was 85.
  7%

• HER2-positive breast cancer [7]: objective response rate (ORR) of 60.
  9% and disease control rate (DCR) of 97.
  3%

• HER2-positive colorectal cancer [8]: Objective response rate (ORR) was 45.
  3% and disease control rate (DCR) was 83.
  0%

Before that, DS-8201 has been approved by the US FDA and Japan for the clinical treatment of breast 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 HER2-mutated patients, including: 7 cases of urothelial carcinoma or Patients with bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer or rare tumors, all patients with at least one disease progression after systemic therapy, and patients who have received prior HER2-targeted therapy are allowed of
.

In this way, we can find that DS-8201 has a lot of "ambition" in the layout of the entire cancer species, which also makes us more confident that the dawn of HER2 mutant patients is not far away, and we believe that with the advancement of multiple clinical trials , more patients will benefit from this "anticancer 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
.

[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