This article comes from the WeChat public account:CC Weekly (ID: cancer-weekly), author: Zhang Hongtao (Associate Professor, School of Medicine, University of Pennsylvania), from the title figure: vision China
Key points:
1. In the clinical trial, the new drug DS-8201 caused 51% of gastric cancer patients to have objective remission, significantly reduced the tumor, and reduced the risk of death by 41%, prolonging the overall overall survival, or will become a special effect drug;
2. Nearly half a million people die of gastric cancer each year in China, accounting for more than half of the global total. DS-8201 will change the current status of treatment of gastric cancer patients in China;
3. The effect of DS-8201 on HER2-positive lung cancer and colon cancer is also “amazing”;
4. DS-8201 is expected to be the next heavyweight HER2 targeted therapy weapon, and it is expected that the FDA will also approve it as a new drug for cancer treatment by the end of June.
At the recently concluded American Society of Clinical Oncology (ASCO) annual meeting, AstraZeneca Pharmaceuticals released several items related to an anti-cancer The clinical trial results of the new drug DS-8201, among which the clinical research of gastric cancer has burst out of popularity, is particularly worthy of attention. In addition to its overwhelming advantages in the treatment of breast cancer and lung cancer, this antibody drug is also in the treatment of gastric cancer With an objective remission rate of 51%, and a 41% reduction in the risk of death, it has become a dark horse in the treatment of gastric cancer.
According to this result, FDA is expected to approve DS-8201 as a new treatment for gastric cancer around the end of June.
What does the gastric cancer clinical trial say, 51% is effective, what does it mean?
This clinical trial of gastric cancer is an open-label, randomized phase 2 clinical trial, testing a DS-8201(Enhertu) New medicine for span>. A total of 187 HER2-positive patients have received more than one line of treatment before, and after treatment, they have relapsed or their disease has progressed. Now they are included in the DS-8201 group and the chemotherapy group at a 2:1 ratio. Receive two different treatments. The primary endpoint of clinical trials is the improvement in objective response rate, and the secondary endpoints are overall survival, progression-free survival in response time, safety, and so on.
As the primary response rate, the objective remission rate of the DS-8201 group reached 51%, indicating that half of the patients had objective remission after treatment, and the tumor had significantly reduced. In contrast, the objective response rate of the chemotherapy control group was only 14%. None of the patients in the chemotherapy group had complete remission, but in the DS-8201 treatment group, 11% of the patients had complete remission, that is, the tumor completely disappeared.
Overall survival is the gold standard for cancer treatment. This clinical trial is relatively low-key and does not use overall survival as the main endpoint. However, the actual result should be much higher than expected. The advantage of DS-8201 is also seen in overall survival: treatment group The median overall survival was 12.5 months, compared with 8.4 months in the control chemotherapy group. Compared with chemotherapy, DS-8201 reduced the risk of death by 41%!
total survival curve (from literature [1])
From the perspective of treatment effect, DS-8201 is better than chemotherapy. From the perspective of safety, the side effects of DS-8201 are also greater, mainly manifested in the side effects on cells such as neutrophils, platelets, and white blood cells. The results of this study were also published in the [1] in the New England Journal of Medicine.
Nearly 500,000 people in China die of gastric cancer, more than half of global cancer deaths
DS-8201 will change the status of gastric cancer treatment without new drugs available
Stomach cancer cases worldwide, mainly in East Asia. In European and American countries, although gastric cancer was the most common cancer 100 years ago, it has become a relatively rare type.
The death of gastric cancer mainly occurs in China. Every year, nearly 500,000 people die of gastric cancer in China, accounting for about half of the global gastric cancer deaths [2,3].
For every five patients with advanced gastric cancer, one is HER2 positive. Before, for these patients, the anti-HER2 antibody drug trastuzumab combined with chemotherapy has become a first-line treatment. In targeted treatment of breast cancer, trastuzumab shines, but for gastric cancer, the efficacy is very limited. Compared with chemotherapy, Herceptin combined with chemotherapy only improves the median overall survival from 11.1 months to 13.8 months, and once the patient is resistant to Herceptin, there is no standard treatment plan and can only be used in turn Various chemotherapy with limited efficacy.
DS-8201 is a new generation antibody-drug conjugate(ADC), directly put a chemotherapy drug (topoisomerase 1 inhibitor deruxtecan) Hang on Trastuzumab, the anti-HER2 antibody. Because of this plug-in, antibodies can deliver cytotoxic chemotherapy drugs directly to cancer cells, which greatly increases the anti-cancer effect. DS-8201 has received FDA accelerated/conditional approval at the end of last year for the treatment of patients with advanced HER2-positive breast cancer who have been treated with ≥ 2 anti-HER2 drugs. The official drug name of DS-8201 is Enhertu, pronounced “摁HER2”. Pressing is a verb. In Chinese, it means to press or press by hand, which means “press HER2 hard on the ground and rub it”.
The DS-8201 clinical study currently published on ASCO, although only a Phase 2 clinical study, its significance is self-evident. At present, the clinical research of gastric cancer is carried out in Asia, mainly in patients of Japan and South Korea. Because gastric cancer is already a rare cancer in Europe and the United States, it is impossible to carry out large-scale therapeutic clinical trials. So it is very likely that FDA will directly DS-8201 was approved as a gastric cancer drug, so that advanced patients with HER2-positive use above the second line.
DS-8201 has a “surprising move” in the treatment of HER2-positive lung cancer and colorectal cancer
The just-concluded 2020 ASCO conference also reported the clinical research progress of DS-8201 in lung cancer and colorectal cancer.
Some patients with non-small cell lung cancer (NSCLC) who carry HER2mutation. For such patients who have received one or more systemic treatments but have disease progression, a phase II clinical trial of DS-8201(DESTINY-Lung01)< /span>The results show that after receiving DS-8201 monotherapy, patients can achieve an objective response rate of 61.9% (ORR), the median is no progress The survival period (PFS) is 14.0 months.
For both men and women, Lung cancer ranks first in cancer mortality, accounting for about one-fifth of all cancer deaths in the world. 80% to 85% of lung cancers are non-small cell lung cancers, and HER2 mutations account for about 2% to 4% of non-small cell lung cancers. There is currently no officially approved drug for the treatment of HER2 mutant non-small cell lung cancers.
In another clinical trial of advanced colorectal cancer, (DESTINY-CRC01), DS-8201 also showed very good result. This is a phase II, open-label, multi-center clinical study. The patient is HER2-positive/RAS wild-type metastatic colorectal cancer. The posterior line is (≥3 lines) treatment. (HER2 IHC 3+ or IHC 2+/FISH+) in patients with high HER expression, the objective response rate after DS-8201 treatment is 45.3 %, the median PFS was 6.9 months, and one of the patients had a complete remission.
In the studyIn the case, even if the patient has used other HER2 targeted therapy before, it still does not affect the benefit of DS-8201 treatment, and the ORR is still 43.8%. However, if there is low or no expression of HER2, the patient has no therapeutic effect after receiving DS-8201 treatment, and no case has objective remission. In the course of treatment, 5 patients developed interstitial lung disease (ILD), and 2 of them died as a result, so the safety issue also deserves attention.
From the results of these clinical studies, DS-8201 will properly become the next heavy weapon of targeted HER2 therapy. In addition to breast cancer that has been approved, gastric cancer will also be an important indication for DS-8201. Relatively speaking, there are fewer patients with lung cancer and colon cancer, but after all, there is a silver lining.
Of course, as an antibody with a chemotherapeutic agent, it is also necessary to prepare for the safety of DS-8201. Patients need to pay attention to the related side effects in time to avoid adverse events.
References:
1. Shitara, K., et al., Trastuzumab Deruxtecan in Previously TreatedHER2-Positive Gastric Cancer. New England Journal of Medicine, 2020.
2. Chen, W., et al., Cancer statistics in China, 2015. CACancer J Clin, 2016. 66(2): p.115-32.
3. Feng, R.-M., et al., Current cancer situation in China: goodor bad news from the 2018 Global Cancer Statistics? CancerCommunications, 2019. 39(1 ): p. 22.
This article comes from the WeChat public account:CC Weekly (ID: cancer-weekly) author: Zhang Hongtao (Associate Professor, School of Medicine, University of Pennsylvania)