Trastuzumab deruxtecan beats chemotherapy—even in HER2-ultralow MBC | ASCO 2024

Background

HER2 has long been a target in breast cancer treatment. Drugs that target HER2 typically work against breast cancers that have HER2 levels of 2+ in laboratory tests.

Two years ago, the groundbreaking DESTINY-Breast04 clinical trial reported that a drug in this family, the antibody-drug conjugate trastuzumab deruxtecan (also known as Enhertu or T-DXd), was more effective than chemotherapy as a second treatment. Even more significantly, it was effective against HER2-low breast cancers. This study changed the way doctors think about HER2 status.

In the past, doctors defined breast cancer as HER2-positive or HER2-negative. With the DESTINY-Breast04 trial results, the definition of HER2-low emerged. HER2-low breast cancers have HER2 levels between 1 and 2. This news opened the door to a new second-line treatment option for many people with metastatic breast cancer, including some with triple-negative breast cancer.

Now, the DESTINY-Breast06 clinical trial takes this area of research a step further to test trastuzumab deruxtecan in people with both low and ultralow HER2 levels who have not had chemotherapy. In this trial, HER2-ultralow is defined as HER2 levels between 0 and 1.

Results

DESTINY-Breast06 results show that trastuzumab deruxtecan is a more effective first treatment for HER2-low, hormone receptor-positive metastatic breast cancer than chemotherapy. Participants who received trastuzumab deruxtecan went on average five months longer without cancer growth or spread than those receiving chemotherapy. Early results show similar benefit in HER2-ultralow breast cancers. The benefit was seen across subgroups.

DESTINY-Breast06 is a phase III open-label study in which 866 people with hormone receptor-positive metastatic breast cancer were randomized to one of two groups: one that received trastuzumab deruxtecan and one that received chemotherapy chosen by the doctor. Most people in the chemotherapy group were given the chemotherapy capecitabine (Xeloda). Some received nab-paclitaxel (Abraxane) or paclitaxel (Taxol). Importantly, participants had not had prior chemotherapy. All had HER2 levels in the low or ultralow range.

Despite its effectiveness, trastuzumab deruxtecan brings a higher risk of serious side effects than chemotherapy. Of greatest concern is the risk of interstitial lung disease. Nausea was the most common side effect experienced by people in the trastuzumab deruxtecan group.

What does this mean for you?

If you have been diagnosed with hormone receptor-positive metastatic breast cancer and have not started treatment, talk with your doctor about these results. Endocrine therapy is still the primary treatment for hormone receptor-positive breast cancers. Your doctor’s recommendation for treatment after endocrine therapy may change based on this study.

If you have had a HER2 test that shows any HER2 level, you might be eligible for trastuzumab deruxtecan. HER2 tests can produce different results, but even one positive test is enough for trastuzumab deruxtecan eligibility. If HER2 testing was negative in the past, talk with your doctor about having a follow-up test.

Although trastuzumab deruxtecan is generally considered safe, it can cause serious side effects. If you are taking this drug, be sure to report any changes you notice to your healthcare team right away.

DESTINY-Breast06 also raised questions about the value of HER2 testing before using trastuzumab deruxtecan. As more people meet criteria for trastuzumab deruxtecan, how important is it to test HER2 status before trying this medicine? According to LBBC Medical Advisory Board member Rita Nanda, MD, “I suspect that we will get to a place where we don’t even need to check with a HER2 IHC test, and we will just give trastuzumab deruxtecan to everyone. There is an ongoing trial to evaluate this question specifically.”

Learn more: Join Dr. Nanda and the LBBC team at our free June 13 webinar, Updates from the 2024 ASCO Annual Meeting.

The DESTINY-Breast06 trial did not include people with hormone receptor-negative breast cancer. DESTINY-Breast15 is a new clinical trial that is open to people with hormone receptor-positive and hormone receptor-negative breast cancer. This trial is recruiting participants now.