And the good news extends far beyond breast cancer. Evidence suggests that the drug could one day be used to treat many other types of tumors, opening wide opportunities for Enhertu and other similar drugs.
Enhertu is called an antibody-drug conjugate because it uses an antibody to focus on a tumor cell before releasing a toxic chemotherapy payload to kill it. The antibody in this drug focuses on a protein called HER2, a growth signal that in some breast cancers becomes over-amplified. The U.S. Food and Drug Administration approved Enhertu in late 2019 for certain so-called “HER2-positive” cancers, or tumors that, on a diagnostic test, show a certain threshold of this signal.
The new data comes from breast cancers that have low or even negligible levels of HER2. This means that a much wider range of patients could benefit from the drug – up to 55% of breast cancers that were previously considered ‘HER2 negative’ could actually have these low levels of the protein.
Other HER2-targeting drugs have been studied in patients whose tumors express low levels of the protein, but none have helped. Oncologists have a few theories about what makes Enhertu different.
One possibility is that there is just enough HER2 expressed on the surface of the cancer cell to make it “sticky” enough for the Enhertu antibody to attach and then deliver the powerful chemo.
Another idea relates to the inherent variability of tumors. “When you look at breast cancers under a microscope, not all cells are the same,” says Harold Burnstein, a breast cancer specialist at the Dana Farber Cancer Institute in Boston. If enough cells with HER2 on the surface can attract the drug to the tumor, chemo can also kill nearby cancer cells that lack the key protein.
The design of the drug itself might also matter. Daiichi Sankyo, who discovered the drug before striking a deal to develop it with AstraZeneca in 2019, appears to have resolved many issues that limited the success of earlier antibody-drug conjugates. Enhertu uses a different, more powerful, and larger chemo payload as well. While most antibody-drug conjugates carry two to four chemo molecules, Enhertu delivers eight. The payload effect is also more short-lived, to help minimize the side effects of highly toxic chemo.
This suggests that after decades of trial and error with antibody-drug conjugates, cancer researchers are finally beginning to understand how best to design and use them.
And the success of this trial could mean the drug will be used far beyond breast cancer. Many other types of tumors express low levels of HER2, including stomach, colon, and lung cancers. AstraZeneca is currently studying Enhertu in these cancers. “The benefit of this drug is not yet fully realized,” says Burnstein.
The evidence adds to a growing body of research suggesting that antibody-drug conjugates will one day replace conventional chemotherapy for most patients, says Maryam Lustberg, chief of breast medical oncology at Yale Cancer Center.
Medications are not without drawbacks. Enhertu’s design allows the use of otherwise too toxic chemotherapy, but the side effects of the drug – and of antibody-drug conjugates in general – are similar to those of any chemotherapy. And these drugs are much more expensive, potentially putting them out of reach for uninsured people or breast cancer patients in low-income countries.
Nonetheless, Enhertu is teaching the field how to design drugs in this class to maximize their benefits. This could mean effective treatment for a wide universe of patients.
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This column does not necessarily reflect the opinion of the Editorial Board or of Bloomberg LP and its owners.
Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, healthcare, and pharma. Previously, she was the editor of Chemical & Engineering News.
More stories like this are available at bloomberg.com/opinion
