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Although HER2 targeted therapy has changed the treatment of breast and gastric cancer patients, HER2 targeted therapy has not yet been approved for non-small cell lung cancer patients
.
Therefore, such patients usually use standard chemotherapy or immunotherapy, but the effect is not satisfactory
In addition, only 27% of patients in this population have an objective response to immune checkpoint inhibitors, and most patients have a poor response
.
Trastuzumab-drutecan (ds-8201) is a humanized anti-HER2 monoclonal antibody (trastuzumab) composed of an antibody-conjugated drug (ADC), a cleavable tetrapeptide-based linker and a cytotoxic topology including one Isomerase inhibitor (DXd) prevents tumor cell DNA replication and leads to tumor cell death
.
Structure of trastuzumab-drutecan (DS-8201)
Trastuzumab has been approved for the treatment of her2-positive metastatic breast cancer and gastric cancer
.
So, are ADC drugs equally effective against HER2 mutant non-small cell lung cancer?
On September 18, 2021, researchers from the Dana-Farber Cancer Institute in the United States published a titled "Trastuzumab Deruxtecan in her2 mutant" in the New England Journal of Medicine (NEJM).
Non-Small" paper, this is the first research paper on cell lung cancer among four major international medical journals
In this multicenter international trial of patients with advanced HER2 mutant non-small cell lung cancer, trastuzumab-drutecan treatment showed a high response rate and prolonged the survival of patients, only 2% of patients occurred A fatal incident
.
However, 20% of patients develop interstitial lung disease, which requires careful safety monitoring and management
.
In summary, this study provides direct evidence for the long-lasting anti-cancer activity of ADC drugs in such lung cancer patients
From May 30, 2018 to July 21, 2020, the research team recruited 91 patients with HER2 mutant non-small cell lung cancer and treated them with trastuzumab-drunotecan
.
Among 91 patients, 1 patient (1%) had a complete remission, 49 patients (54%) had a partial remission, and the vast majority of patients (92%) had tumor shrinkage
Of the 33 patients with central nervous system metastases at the baseline examination, 14 received brain radiotherapy and 19 did not receive radiotherapy
.
Among these patients, 8 and 10 patients had partial remissions, respectively
A total of 47 patients (52%) died
.
The 91 patients had a median remission period of 9.
At least one adverse event occurred in 88 patients (97%), and the research team reported that these events were related to trastuzumab-drutecan
.
47% of patients had minor adverse events, such as gastrointestinal bleeding, loss of appetite, and hair loss, 18 patients (20%) had serious adverse events, such as interstitial lung disease, and 2 patients had fatal adverse events
.
After treatment, 24 patients developed interstitial lung disease or lung scars
.
Therefore, the research group stopped the treatment of 16 patients and stopped the treatment of 8 patients
.
Patients in this condition receive steroid therapy
.
In summary, these data indicate that HER2 mutation can be used as a therapeutic target in non-small cell lung cancer, and trastuzumab-drutecan showed durable resistance in 91 patients with HER2 mutation in non-small cell lung cancer
.
Cancer activity: 55% of patients have a proven objective treatment effect
.
The median duration of efficacy was 9.
3 months, the median progression-free survival was 8.
2 months, and the median overall survival was 17.
8 months
.
These results support the use of trastuzumab to treat patients with HER2 mutant non-small cell lung cancer
.
The clinical trial was funded by Daiichi Sankyo and AstraZeneca
.
Trastuzumab-drutecan (DS-8201) was developed by Japan's Daiichi Sankyo Pharmaceutical Company
.
In March 2019, AstraZeneca and Daiichi San signed a total of US$6.
9 billion in global joint development and commercial cooperation agreements
.
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