Antibody drug increases survival in advanced breast cancer

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By Dennis Thompson

Health Day Reporter

THURSDAY, December 8, 2022 (HealthDay News) — A relatively new drug is increasing survival rates for women with a certain type of advanced breast cancer who have failed other treatments, according to two clinical studies.

The targeted antibody drug – trastuzumab deruxtecan (T-DXd, sold under the brand name Enhertu) – dramatically outperformed an older antibody drug in one study, quadrupling the number of months women lived without their cancer getting worse.

T-DXd also outperformed standard chemotherapy in another clinical study, more than doubling the number of months of progression-free survival and reducing the risk of death by 34%.

T-DXd aims to help patients with HER2-positive breast cancer.

HER2 is a protein that promotes the growth of breast cancer cells. About 20% of patients have tumors with higher levels of HER2.

Results from both clinical trials were presented Wednesday at the San Antonio Breast Cancer Symposium.

“We have a drug that is very effective and appears to work at least in part through a targeting mechanism against HER2,” said Dr. Carlos Arteaga, Chair of Comprehensive Oncology at Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, in Dallas.

Arteaga, co-director of the symposium, chaired a press conference announcing the results of the two studies.

T-DXd deals a double whammy to breast cancer cells by combining an antibody called trastuzumab with a chemotherapy drug called deruxtecan.

The antibody portion of T-DXd binds to HER2 receptors on the breast cancer tumor, blocking the protein’s ability to promote cancer growth. This binding also serves to target the cancer-killing deruxtecan directly into the tumor cells.

The US Food and Drug Administration approved T-DXd in 2019 as a follow-up therapy for patients whose breast cancer had spread despite previous treatment with other anticancer drugs.

Ongoing clinical trials aim to find out how effective T-DXd is compared to other drugs and when it should be used to treat advanced HER2-positive breast cancer.

A clinical study compared T-DXd as a follow-up treatment to trastuzumab emtansine (T-DM1), a previous antibody drug that combined trastuzumab with another chemotherapy drug.

The 524 patients in this study were randomly assigned to receive either drug after they failed to respond to initial therapies.

About one in five patients (21%) became cancer-free after treatment with T-DXd, compared with almost 10% of patients who received T-DM1, the researchers reported.

In addition, more than 78% showed some clinical response to T-DXd compared to 35% who responded to T-DM1.

Patients treated with T-DXd had an average of almost 29 months progression-free survival, about four times the 7 months for patients who received T-DM1, sold under the brand name Kadcyla.

Patients who received T-DXd also had a 36% lower risk of all-cause death than patients treated with T-DM1, said clinical trials investigator Dr. Sara Hurvitz, a professor at the University of California, Los Angeles, the Geffen School of Medicine and the Jonsson Comprehensive Cancer Center.

“These updated results show remarkable benefits (overall survival) and (progression-free survival) and solidly place T-DXd as the standard of care,” Hurvitz said in a news conference.

The other clinical study compared T-DXd to standard chemotherapy as a follow-up treatment.

The study involved more than 600 patients whose breast cancer had worsened after treatment with T-DM1. About two-thirds received T-DXd and the remainder received chemotherapy.

The researchers found that breast cancer patients were 64% less likely to die or have their cancer spread after treatment with T-DXd compared to chemotherapy

Median progression-free survival with T-DXd was nearly 18 months, more than double the 7 months achieved with chemotherapy.

Overall survival was also significantly longer, an average of 39 months for T-DXd patients compared to 26 months with chemotherapy.

About 14% of patients became cancer-free after T-DXd treatment in this study, compared to 5% with chemotherapy.

The study “confirms the favorable benefit-risk balance of T-DXd in patients with HER2-positive advanced breast cancer,” said clinical trial investigator Dr. Ian Krop, Chief Clinical Research Officer at Yale Cancer Center in New Haven, Connecticut.

In both studies, the most worrying side effect of T-DXd was damage to the lungs, either through inflammation or scarring of the lung tissue.

About 6% developed pneumonia and 3% lung scarring in Krop’s study, while about 15% developed pneumonia or scarring in Hurvitz’s study.

It’s not yet clear why the drug would cause these side effects in the lungs, Hurvitz said, noting that it doesn’t appear to be driven by the cancer’s spread to the lungs.

“We as clinicians should continue to closely monitor the CT scans of the lungs in our patients treated with T-DXd, as this is an event that can occur even up to a year or more after a patient has received therapy has,” Hurvitz said.

Results presented at medical congresses should be considered preliminary until published in a peer-reviewed journal.

More information

The American Cancer Society has more on HER2 positive breast cancer.

SOURCES: Carlos Arteaga, MD, Chair, Comprehensive Oncology, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas; Sara Hurvitz, MD, Professor, University of California, Los Angeles, David Geffen School of Medicine and Jonsson Comprehensive Cancer Center; Ian Krop, MD, PhD, Chief Clinical Research Officer, Yale Cancer Center, New Haven, Connecticut; Presentation, San Antonio Breast Cancer Symposium, December 6-10, 2022


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Antibody drug increases survival in advanced breast cancer
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