This drug could change the way breast cancer is treated

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New data on a breast cancer treatment from AstraZeneca and Japanese drugmaker Daiichi Sankyo drew a standing ovation from cancer doctors attending their annual meeting in Chicago on Sunday. And for a good reason.

The drug Enhertu enabled women with advanced breast cancer to live six months longer than others treated with conventional chemotherapy. Oncologists are calling the results “practice change” for metastatic breast cancer.

And the good news goes well beyond breast cancer. The evidence suggests the drug could one day be used to treat many other types of tumors — opening up broad possibilities for Enhertu and other similar drugs.

Enhertu is what’s called an antibody-drug conjugate because it uses an antibody to target a tumor cell before releasing a payload of toxic chemotherapy to kill it. The antibody in this drug targets a protein called HER2, a growth signal that is over-amplified in some types of breast cancer. The U.S. Food and Drug Administration approved Enhertu in late 2019 for some so-called “HER2-positive” cancers or tumors that show a certain threshold of this signal in a diagnostic test.

The new data come from breast cancers with low, even negligible, levels of HER2. That means a much wider range of patients could benefit from the drug — up to 55% of breast cancers previously thought to be “HER2-negative” could actually have these low protein levels.

Other HER2-targeted 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 just enough HER2 is expressed on the cancer cell’s surface to make it “sticky” enough for Enhertus antibodies to attach and then deliver the powerful chemotherapy.

Another idea relates to the inherent variability of tumors. “When you look at breast cancer under a microscope, not every cell is 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, chemotherapy can also target nearby cancer cells that lack the key protein.

The design of the drug itself could also play a role. Daiichi Sankyo, who discovered the drug before it signed a deal to develop it with AstraZeneca in 2019, appears to have ironed out many of the kinks that limited the success of previous antibody-drug conjugates. Enhertu uses a different, more powerful chemo payload, and also a larger one. While most antibody-drug conjugates carry two to four chemomolecules, Enhertu delivers eight. The payload’s effect is also more volatile to minimize the side effects of highly toxic chemotherapy.

This suggests that after decades of trial and error with antibody-drug conjugates, cancer researchers are finally beginning to understand how best to develop and use them.

And the success of this study could mean that the drug will be used well beyond breast cancer. Many other types of tumors express low levels of HER2, including gastric, colon, and lung cancers. AstraZeneca is now studying Enhertu in these cancers. “The benefit of this drug has yet to be fully realized,” says Burnstein.

The evidence adds to a growing body of research suggesting that antibody-drug conjugates will one day replace traditional chemotherapy for most patients, says Maryam Lustberg, director of medical oncology for breast cancer at Yale Cancer Center.

The drugs are not without their downsides. Enhertu’s design allows for the use of otherwise overly toxic chemotherapy, but the side effects of the drug — and antibody-drug conjugates in general — are similar to those of all chemotherapy. And these drugs are much more expensive, potentially making them out of reach for the uninsured or breast cancer patients in low-income countries.

Nonetheless, Enhertu teaches the field how drugs in this class are designed to maximize their utility. This could mean an effective treatment for a wide range of patients.

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This column does not necessarily represent the opinion of the editors or of Bloomberg LP and its owners.

Lisa Jarvis is a columnist for Bloomberg Opinion, covering biotechnology, healthcare and the pharmaceutical industry. Previously, she was Editor-in-Chief of Chemical & Engineering News.

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