Breast cancer drug Enhertu leads to 'unprecedented' survival rates

The patients had metastatic breast cancer that had progressed despite cycles of severe chemotherapy. But treatment with a drug that tar...


The patients had metastatic breast cancer that had progressed despite cycles of severe chemotherapy. But treatment with a drug that targeted cancer cells with laser-like precision was surprisingly successful, slowing tumor growth and extending life to an extent rarely seen with advanced cancers.

The new study, presented at the annual meeting of the American Society of Clinical Oncology and published Sunday in the New England Journal of Medicinewould change the way medicine was practiced, cancer experts have said.

“This is a new standard of care,” said breast cancer specialist Dr. Eric Winer, director of Yale Cancer Center and head of ASCO. Dr. Winer was not involved in the study. He added that “it affects a large number of patients”.

The trial focused on a particular mutant protein, HER2, which is a common villain in breast cancer and other cancers. Drugs that block HER2 have been incredibly effective in treating breast cancers that are almost entirely populated by the protein, transforming HER2-positive breast cancers from those with some of the worst prognoses to those where patients do very well. good.

But HER2-positive cases only make up about 15 to 20 percent of breast cancer patients, said Dr. Halle Moore, director of breast medical oncology at the Cleveland Clinic. Patients with only a few HER2 cells – a condition known as HER2-low – were not helped by these drugs. Only a small proportion of their cancer cells had HER2, while other mutations were primarily responsible for cancer growth. And that was a problem because the cancer cells escaped the chemotherapy treatments.

The clinical trial, sponsored by pharmaceutical companies Daiichi Sankyo and AstraZeneca and led by Dr. Shanu Modi of Memorial Sloan Kettering Cancer Center, involved 557 patients with metastatic breast cancer who were HER2-low. Two-thirds took the experimental drug, trastuzumab deruxtecan, sold as Enhertu; the rest suffered standard chemotherapy.

In patients who took trastuzumab deruxtecan, tumors stopped growing for about 10 months, compared to 5 months for those who received standard chemotherapy. Patients with the experimental drug survived for 23.9 months, compared to 16.8 months for those who received standard chemotherapy.

“It is unprecedented that chemotherapy trials in metastatic breast cancer improve patient survival by six months,” said Dr. Moore, who recruited some patients into the study. Usually, she says, success in a clinical trial results in a few extra weeks of life or no survival benefit, but an improvement in quality of life.

The results were so impressive that the researchers received a standing ovation when they presented their data at the oncology conference in Chicago on Sunday.

Trastuzumab deruxtecan was already approved for patients with HER2-positive breast cancer, but few expected it to work because other drugs for these cancers had failed in HER2-low patients.

The drug consists of an antibody that searches for the HER2 protein on the cell surface. The antibody is attached to a chemotherapy drug. When trastuzumab deruxtecan finds a cell with HER2 on its surface, it enters the cell and the chemotherapy drug separates from the antibody and kills the cell.

But “what’s unique and distinct” about trastuzumab deruxtecan, adds Dr. Modi, is that the chemotherapy drug seeps through the cell membrane. From there, it can travel to nearby cancer cells and kill them as well.

Like all chemotherapies, trastuzumab deruxtecan has side effects including nausea, vomiting, blood disorders and, most notably, lung damage that led to the death of three patients in the trials.

But, Dr. Winer said, “if I were a patient with metastatic breast cancer, and if I had to take a drug with the side effects of chemotherapy, I would prefer this drug.”

The doctors said they plan to try the treatment in their breast cancer patients with HER2-low metastatic cancers.

“We’re all going back and looking at our patients right now,” said Dr. Susan Domchek, a breast cancer specialist at the University of Pennsylvania’s Abramson Cancer Center. She says that even before the Food and Drug Administration approves trastuzumab deruxtecan for HER2-low patients, she’ll see if the data from the new study will be enough to convince insurers to approve the drug, which comes at a price. wholesale of about $14,000 every three weeks.

Dr. Winer emphasized that trastuzumab deruxtecan is not a drug for early stage breast cancer; it has yet to be tested in this group of patients. But that’s likely a next step, as is testing the drug in other cancers and expanding its strategy beyond HER2.

“This strategy is the real breakthrough,” he said, explaining that it would allow researchers to zoom in on molecular targets on tumor cells that were only sparsely present.

“It’s not just about this drug or even breast cancer,” Dr. Winer said. “Its real benefit is that it allows us to deliver powerful therapies directly to cancer cells.”

One patient in the ongoing study, Mary Smrekar, 55, of Medina, Ohio, said she felt she had been granted a temporary reprieve from certain death.

She was diagnosed with breast cancer in 2010 and underwent surgery, chemotherapy and radiation therapy. His cancer went into remission.

“I thought I was free and clear,” she said.

But in 2019, the cancer returned. It had spread to her pelvis. She had chemotherapy, but this time there was little improvement.

Two years ago, she participated in the trial at the Cleveland Clinic site. His cancer has not gone away, but the tumors have stopped growing.

“I’m so happy to have had two more years,” Ms Smrekar said. “My daughter is getting married next month. I didn’t think I would go to the wedding.

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Newsrust - US Top News: Breast cancer drug Enhertu leads to 'unprecedented' survival rates
Breast cancer drug Enhertu leads to 'unprecedented' survival rates
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