Datopotamab deruxtecan works better than chemo, with fewer side effects | SABCS 2023

Background

Hormone receptor-positive, HER2-negative breast cancer is the most common type of breast cancer. Treatment for late-stage disease often involves a combination of endocrine therapy and CDK 4/6 inhibitor drugs. Even with multiple treatment options available, the cancer can become treatment resistant. Doctors continue to look for new options for this patient population.

For cancers that do not respond to endocrine therapy, chemotherapy is often the standard treatment. Yet, at this stage of disease, chemotherapy does not work for many and causes side effects that lower quality of life. The past year has brought new FDA approvals — including elacestrant and capivasertib — with additional promising drugs under study.

Datopotamab deruxtean (Dato-DXd) is an antibody drug conjugate that targets TROP2, a glycoprotein that is active in cell signaling pathways and leads to cancer growth. As a targeted drug, Dato-DXd can treat cancer with less harm to healthy cells and potentially fewer side effects than chemotherapy. It is also being studied in non-small cell lung cancer.

Results

TROPION-Breast01 is a randomized, phase III, open-label, international clinical trial comparing datopotamab deruxtecan (Dato-DXd) to chemotherapy. The main results of the study, presented at a recent meeting of the European Medical Society, favored Dato-DXd. Participants taking Dato-DXd went nearly seven months without cancer progressing compared to 4.5 months for participants receiving chemotherapy. This update provides information on subgroups, side effects, and quality of life.

The superiority of Dato-DXd was seen across subgroups:

• People in the Data-DXd group went longer before trying a next therapy compared to people in the chemotherapy group.
• The amount of time on CDK 4/6 inhibitors prior to this clinical trial did not affect response to Dato-DXd. People who took CDK 4/6 drugs for more than a year had similar results to those who took CDK 4/6 inhibitors for less than a year.
• Only a small number of participants in this study had brain metastases at the start of the trial but those who did also saw a better response from Dato-DXd.

This study also looked at quality of life, finding that people who were treated with Dato-DXd had better overall quality of life than those who had chemotherapy. Specifically:

• Only 21% of people in the Data-DXd group had moderate or severe side effects of any kind, compared to 45% in the chemotherapy group.
• More people in the chemotherapy group reduced, paused, or stopped taking the medicine due to side effects.
• Neutropenia, which increases risk of infection, was the most common side effect experienced by people in the chemotherapy group with nearly one-third moderately or severely affected.
• In the Data-DXd group, mild mouth sores or swelling (stomatitis or oral mucositis) was the most common side effect.

Knowing that even mild mouth sores can be very bothersome, the study authors delved further to see how the two treatments affected overall quality of life. Most people feel worse than normal during cancer treatment. How much worse and when the decline starts can offer more insight into the experience. In this study, Data-DXd delayed a decline in quality of life compared to chemotherapy, and quality of life for people in the Data-DXd treatment group remained better over time. Results for physical functioning and pain also showed a delay in decline with Data-DXd.

What does this mean for you?

If you have been diagnosed with hormone receptor-positive, HER2-negative metastatic breast cancer that no longer responds to endocrine therapy, ask about Data-DXd. According to these results, it is both more effective and easier to tolerate than chemotherapy. Although this is a targeted drug, a biomarker test is not required for its use at this time. So far, research has not shown a stronger effect when the TROP2 biomarker is present.

The potential FDA approval of Data-DXd was not discussed in this presentation, although it seems likely. There was also no discussion of how this drug might compare to other antibody-drug conjugates, rather than just chemotherapy. As you make treatment choices, ask about all of your options and their relative risks and benefits.

Note: This clinical trial’s inclusion of quality of life as an outcome is commendable, and the result of years of patient advocacy. Keep up the good work!