Trial Establishes New Standard of Care for Patients with Breast Cancer in "Practice-Changing"

A medication that will revolutionise medical practice will alter the way doctors see metastatic breast cancer.

New data using Enhertu (fam-trastuzumab deruxtecan-nxki), an antibody-drug conjugate (ADC), in patients with HER2-low metastatic breast cancer with both hormone receptor-positive and negative disease were presented by AstraZeneca and Daiichi Sankyo at the American Society of Clinical Oncology (ASCO) annual meeting in June. The usage of Enhertu increases progression-free survival as well as overall survival when compared to chemotherapy alone, according to a study in which patients were randomly assigned to either Enhertu or chemotherapy.

A particular protein called HER2 promotes the growth of breast cancer cells. Oncologists use the HER2 gene, which has a significant impact on breast cancer development, to assist and guide therapy decisions. HER2 protein overexpression or gene amplification are symptoms of HER2-positive breast cancer. The patient would have a tumour with a HER2 negative diagnosis, implying that HER2-targeted therapy would not be an option for treatment if there were only low amounts or no HER2 proteins discovered in the tumour sample.

Before the development of this medication, HER2 expression in metastatic breast cancer was thought to be either positive or negative. However, HER2-low is now the third choice.

Given that the work done in this study concentrated on Enhertu's effects on this patient population, HER2-low will now be acknowledged as a distinction for breast cancer patients. These patients exhibit a higher expression of that protein compared to HER2-negative disease but a lower level compared to HER2-positive disease.

This suggests that some patients with metastatic breast cancer who were once thought to be HER2-negative may actually be HER2-low. According to the trial's abstract, "approximately 55 per cent" of patients with metastatic breast cancer who are "usually classed as HER2-negative express modest levels of HER2."

Enhertu is anticipated to become the new standard of therapy for patients with HER2-low metastatic breast cancer as a result of the DESTINY-Breast04 clinical trial's effectiveness, assuming FDA approval.

Findings Deserving of a Standing Ovation

Medical oncologist Dr. Eleonora Teplinsky, who focuses on breast and gynaecologic cancer, has attended ASCO meetings for more than ten years. Before the plenary session, when the findings of the DESTINY-Breast04 research were revealed, no one at the conference was aware of any specifics about a potential advancement in breast cancer therapies, she told BioSpace.

Oncologists, researchers, patient activists, and business experts gathered to hear Dr. Shanu Modi, M.D., the study's primary author, deliver the findings as they were concurrently published in the New England Journal of Medicine. According to Modi, this trial demonstrated a "statistically significant and clinically relevant advantage" in progression-free survival and overall survival for metastatic breast cancer patients with HER2-low cancer compared to standard-of-care treatment.

The DESTINY-Breast04 results, according to Modi, "are practice-changing."

The survival rate for almost half of all patients with metastatic breast cancer who are now diagnosed can be improved by this new standard of care.

According to Teplinsky, this information will alter the classification of HER2. Teplinsky

"We will no longer categorise the tumour as HER2-negative when looking at patients with metastatic cancer. It will now either be low, negative, or positive, "she declared.

The oncologists in the audience were so ecstatic about the outcomes that they gave the session a standing ovation at the end.

Teplinsky remarked, "The standing ovation was truly fantastic. "Seeing the thousands of people in the room excited and just energised by these increased outcomes is just wonderful," the speaker said after two years of attending ASCO virtually.

According to Sermo, a physician-focused online forum, the DESTINY-Breast04 abstract had the highest attendance at the conference, drawing 79 per cent of oncologists who indicated an interest in breast cancer data in a poll. The breast cancer research presented at this year's ASCO conference was deemed the most practice-changing by close to 60% of the oncologists who participated in the survey.

Additionally, the National Comprehensive Cancer Network (NCCN) revised its breast cancer recommendations to take into account "compelling" evidence that supports the use of Enhertu in those with metastatic HER2-low breast cancer.

DESTINY-Breast04: The Details

The first Phase III clinical trial of a HER2-directed therapy in patients with metastatic HER2-low breast cancer was the DESTINY-Breast04 trial.

The double-blind trial involved 557 patients with HER2-low metastatic breast cancer from Asia, Europe, and North America who had received one to two prior lines of chemotherapy. Chemotherapy or Enhertu was randomly assigned to patients according to the doctor's preference. Chemotherapy had a median treatment time of 3.5 months and Enhertu treatment time of 8.2 months.

In comparison to patients who had received chemotherapy, hormone receptor-positive and negative HER2-low patients treated with Enhertu had improved progression-free survival and overall survival, according to the study's authors. In comparison to individuals who received standard chemotherapy, those treated with Enhertu demonstrated a 49 per cent lower risk of disease progression and a 36 per cent lower chance of mortality.

Among all 577 patients, the median progression-free survival was 9.9 months for the Enhertu group and 5.1 months for the group receiving the doctor's recommended medication. Patients who were treated with Enhertu had an average survival of 23.4 months as opposed to 16.8 months for all other patients.

With a prior anti-HER2-based regimen or "in the neoadjuvant context and have suffered disease recurrence during or within six months of completing therapy," Enhertu is currently FDA-approved to treat people with unresectable or metastatic HER2-positive breast cancer.

Hormone Receptors: Another Factor to Take into Account

Breast cancer detection and treatment also involve oestrogen and progesterone receptors. One or both of the oestrogen and progesterone receptors, which promote the spread of cancer, are attached to hormone receptor-positive tumours. Hormone receptor-negative cancer is defined as lacking either progesterone or oestrogen receptors.

494 (88.7%) of the 577 individuals who were enrolled in the randomised trial had an illness that was hormone receptor-positive, whereas 63 (11.3%) had a disease that was hormone receptor-negative.

The median progression-free survival for the hormone receptor-positive population receiving Enhertu was 10.1 months as opposed to 5.4 months for those receiving chemotherapy. The median overall survival for Enhertu patients was 23.9 months, compared to 17.5 months for chemotherapy patients.

According to an exploratory examination of the study data, patients who were hormone receptor-negative and received Enhertu had a median progression-free survival of 8.5 months as opposed to 2.9 months when they received standard therapy. According to ASCO, those who received Enhertu had a median overall survival rate of 18.2 months as opposed to 8.3 months for those who received chemotherapy.

The improvement in survival for these individuals is "very, really extraordinary," Teplinsky said, adding that "we're pretty enthused about this data" and "a lot of patients will benefit."

Considering the Future

This work has effectively altered how breast cancer is classified by including HER2-low expression to the existing binary of HER2-positive or -negative. This implies that the number of patients who might benefit from HER2-targeted therapy will increase and that the available therapeutic alternatives will alter.

Teplinsky argued that oncologists should begin considering novel approaches to HER2 analysis and techniques to maximise therapeutic effects.

In advanced breast cancer patients with tumours that are HER2-low and hormone receptor-positive, the DESTINY-Breast06 study is now being conducted to "assess the effectiveness, safety, and tolerability" of Enhertu in comparison to chemotherapy.