An FDA-approved drug showed promising results in another breast cancer trial

A clinical trial with an experimental drug involving 557 patients with metastatic breast cancer has shown remarkable results by slowing tumor growth and prolonging survival, The New York Times (The NYT) reported. 

Breast cancer is the second most common cancer that affects women in the U.S. According to the American Cancer Society's estimates, as many as 287,850 new cases of breast cancer will be diagnosed in the U.S. in 2022 alone and will claim more than 43,000 lives. Among them, there are different and varying types of breast cancer and survival rates.

Over the years, treatment options have also improved beyond chemotherapy and radiation therapy; drugs that can specifically target cancerous cells are also now available. One method of doing so is by targeting the human epidermal growth factor receptor or HER2 protein, common on the surface of cancerous cells. For breast cancer patients who are HER2 positive, these drugs have radically improved prognoses. AstraZeneca and Daiichi Sankyo's FDA-approved drug Enhertu is one such treatment option. 

How does Enhertu work? 

Enhertu is the commercial name of the drug scientists call trastuzumab deruxtecan. The drug is a combination of a monoclonal antibody, trastuzumab, and a chemotherapy drug, deruxtecan, where the latter is chemically attached to the antibody. 

The role of the antibody is to flow through the blood and seek cancerous cells that display the HER2 protein on their surface. Once the antibody finds the protein, it attaches itself to it and then enters the cell. This releases the chemotherapy drug which attacks the cell. Interestingly, once the cell dies, the drug moves onto nearby cells, which are also likely cancerous, and kills them too. 

Due to its effective mode of action, Enhertu was approved by the U.S. Food and Drug Administration (FDA) for HER2-positive breast cancer. However, HER2-positive cancers account for no more than 20 percent of breast cancer patients. Also, a patient can also have a mix of tumors with some being HER2-positive while others are not, a condition known as HER2-low, The NYT reported. 

Enhertu trial for HER2-low

AstraZeneca and Daiichi initiated a trial to test whether Enhertu could be effective in patients who had developed metastatic cancers but were HER2-low. The trial involved 557 patients, two-thirds of which received Enhertu while the remaining received standard chemotherapy as treatment. 

The researchers found that tumors stopped growing for 10 months in patients who received Enhertu while chemotherapy could stop them for only five months. Overall survival in patients who received the experimental drug was 23.9 months as against 16.8 months in those who received chemotherapy. 

Cancer experts who spoke to The NYT hailed the findings of the study, as previous trials have shown survival benefits for only a few weeks. Improvement in survival in metastatic breast cancer by six months is "unheard-of," an expert said. 

The results of the clinical trial were also presented at an oncology conference in Chicago this week and have been published in the New England Journal of Medicine. 

The drug still needs FDA approval for use in HER2-low patients and will not be used for early-stage breast cancer since it has not been tested in this patient group so far. The cost of the drug is a whopping $14,000 every three weeks, The NYT said in its report. Like other chemotherapy drugs, Enhertu's side effects include nausea, vomiting, blood disorders, as well as a risk of lung injuries which also led to the death of three patients during the trial. 

Abstract:

Background:

Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these “HER2-low” cancers.

Results:

Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor–positive disease and 63 (11.3%) had hormone receptor–negative disease. In the hormone receptor–positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P=0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P=0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician’s choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.

Conclusions

In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy.