Updated Results from the DESTINY-Breast01 Study

New classes of pharmaceutical drugs are currently being designed as targeted therapy to treat specific types of cancer. One class of these drugs is called antibody–drug conjugates. Enhertu (trastuzumab deruxtecan) is a new antibody–drug conjugate that works to target specific areas on breast cancer cells that remain in the body after surgery and previous treatments, by binding to the diseased cells and delivering medication directly into them.

In a new trial called DESTINY-Breast01, researchers are studying Enhertu in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. This study is being conducted around the world in multiple centers. Because this new treatment has been found to be safe in earlier phase 1 clinical trials, this phase 2 clinical trial will be done to see how well Enhertu works on challenging HER2-positive metastatic breast cancers. Oncologists will be able to research whether the drug meets specific goals of the treatment. In phase 2 trials, they often look to see if the remaining cancer cells shrink or disappear, and they will look at whether the cancer does not appear bigger, or if it will take more time before cancer recurrence. They will also keep track of whether this medication improves patient quality of life, and see if patients receiving the treatment live longer than most people do without treatment.

This trial is open label, meaning the researchers and participants will know which treatment is being administered.

Enhertu is being studied in patients with HER2-positive metastatic breast cancer, and if the results are positive, this will further support the US Drug and Food Administration (FDA) approval in the United States. Shanu Modi, MD, Medical Oncologist, Breast Cancer, Memorial Sloan Kettering Cancer Center, New York City, discussed the updated long-term safety of this medication and results regarding its effectiveness.

In this study, all patients were required to have metastatic breast cancer that progressed on or after receiving Kadcyla (trastuzumab emtansine), which is a therapy approved by the FDA to treat HER2-positive metastatic breast cancer. Postsurgery, if the early-stage, HER2-positive breast cancer still shows signs of residual disease after neoadjuvant treatment, other treatment options are considered by the physician and the patient. Therefore, Enhertu is being studied.

A total of 253 patients were enrolled in the study and 184 received Enhertu at a dose that depended on weight (5.4 mg/kg). The primary end point or goal of this study was to understand the effect of treatment or objective response rate, meaning the proportion of patients with a tumor size reduction of a predefined amount and for a minimum period of time. Additional end points of the study include duration of response, progression-free survival, which measures how long a person lives without the disease worsening, and overall survival (OS), which measures how long patients who undergo a certain treatment regimen live compared with patients who are in a control group. In a clinical trial, measuring the OS is one main way to see how well a new treatment works.

In this study, patients had received an average of 6 previous lines of treatment for metastatic breast cancer. On average, the median duration of follow-up had increased from 11.1 months to 20.5 months, and 37 (20.1%) patients remained on treatment.

The confirmed objective response rate was 61.4% (12 complete responses) with an average duration of response of 20.8 months. The disease control rate was 97.3%. The updated median progression-free survival was 19.4 months. The estimated OS was 85% at 12 months and 74% at 18 months. The preliminary median OS is 24.6 months. The safety profile of Enhertu was similar to previously reported studies; however, with an additional 9 months of follow-up, only 3 new cases of treatment-related interstitial lung disease were reported.

With results that were similar to previous studies, Enhertu demonstrated high rates of durable responses in a heavily pretreated population of patients with metastatic breast cancer. While the results are preliminary, they are encouraging. These end points and goals will be further studied in the ongoing randomized controlled studies of Enhertu. For patients who remained on treatment for this longer duration, which was double that of the previous report, the rate of discontinuation or interstitial lung disease did not notably increase. Oncologists need to continue paying attention to lung or pulmonary symptoms, and careful monitoring is needed overall.