> HER2-Targeted Therapies Presented at SABCS Move Quickly Through FDA Approval

HER2-Targeted Therapies Presented at SABCS Move Quickly Through FDA Approval


FDA names tucatinib a breakthrough therapy and grants accelerated approval to trastuzumab deruxtecan in weeks after San Antonio Breast Cancer Symposium

Two HER2-targeted therapies have been designated for special approval programs by the U.S. Food and Drug Administration just weeks after results were presented at the 2019 San Antonio Breast Cancer Symposium. The FDA gave accelerated approval to trastuzumab deruxtecan (Enhertu) for certain people with metastatic HER2-positive breast cancer. It also named tucatinib a breakthrough therapy, which is designed to help medicines move more quickly through approval.

The current standard of care for metastatic, HER2-postive breast cancer includes treatment with the targeted therapies trastuzumab (Herceptin) and pertuzumab (Perjeta) with chemotherapy, followed by ado-trastuzumab emtansine (Kadcyla), another targeted therapy, after the cancer grows with the first treatments. After these treatments there is no standard. It’s unclear whether another round of targeted therapy could keep cancer from growing. Both trastuzumab deruxtecan and tucatinib represent possible new treatments for people with this situation.

Breakthrough Therapy designation is an FDA program designed to help treatments that perform better than existing options for serious or life-threatening conditions get through the approval process more smoothly and quickly. It gives the company making the medicine more support from the FDA in preparing and reviewing its application, with the goal of getting accelerated approval.

Trastuzumab Deruxtecan

Daiichi Sankyo announced December 23 that the FDA approved its antibody-drug conjugate trastuzumab deruxtecan to treat people who have metastatic HER2-positive breast cancer and have been through at least two previous lines of treatment. The approval was based on findings from the DESTINY-Breast01 clinical trial.

Antibody-drug conjugates are medicines that pair chemical medicines that kill cells to antibodies that target features of the cancer cells. With trastuzumab deruxtecan, trastuzumab directs the medicine to cancer cells overexpressing the HER2 protein. Another antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla) was approved earlier this year to treat metastatic HER2-positive breast cancers, and researchers hope that newer medicines of this class, like trastuzumab deruxtecan, designed to carry more of the part that kills cells, can produce even better results.


DESTINY-Breast01 was a phase II trial that gave trastuzumab deruxtecan to 184 women with metastatic HER2-positive breast cancer. All the women had already received trastuzumab and ado-trastuzumab emtansine, and their cancers had grown. The trial was open-label, meaning women and their doctors knew they were being given trastuzumab deruxtecan. Everyone in the trial received the study medicine.

Results from DESTINY-Breast01 presented at SABCS 2019 excited researchers with how many women had cancers that responded to the medicine and how long that response lasted, especially among this group that had received all standard treatments:

  • Cancer responded in 60.9 percent of women.
  • The median length of response was 14.8 months.

The most common side effects were nausea, vomiting, and fatigue. The new treatment was also linked to a condition called interstitial lung disease that shows as scarring or inflammation of the lungs. This condition can be fatal, and four women (2.2 percent of participants) in the study died from it. The medicine comes with a warning for doctors to watch for any symptoms of a problem in the lungs and lower the dose or stop treatment with it if interstitial lung disease is suspected.

Trastuzumab deruxtecan was previously named a breakthrough therapy and its approval came through an accelerated process meant to get medicines that show a substantial improvement over existing treatments for serious conditions available sooner.


Just a few days earlier, the HER2-targeted therapy tucatinib was named a breakthrough therapy by the FDA, Seattle Genetics announced. A phase III study found that adding tucatinib to treatment for metastatic, HER2-positive breast cancer led to people going longer without cancer growing and living longer.

Tucatinib is a small-molecule tyrosine kinase inhibitor, a class of medicines made in a lab that target proteins involved in the growth of HER2-positive breast cancers. Because tucatinib is a small molecule, unlike most other molecules used in HER2-positive breast cancer, researchers hope it might cross the blood-brain barrier to treat brain metastases.


In the phase III HER2CLIMB trial — presented at SABCS earlier in December — tucatinib was given with trastuzumab (Herceptin) and capecitabine (Xeloda) to people with metastatic breast cancer who already had cancer grow during past targeted treatments. The study notably included people with brain metastases. They are often excluded from trials, but as a small molecule tucatinib is designed to cross the blood-brain barrier.

Results from the tucatinib group were compared to a control group of people given trastuzumab, capecitabine, and a placebo.

In results reported at SABCS 2019 and published in the New England Journal of Medicine, tucatinib led to people going longer without cancer growing — both in the whole group and in people with brain metastases specifically — and to people living longer:

  • People in the tucatinib group went 2.2 months longer than those in the placebo group without cancer growing.
  • Cancer had not grown in 25 percent of people with brain metastases in the tucatinib group after 1 year, and nobody in the placebo group went a year without cancer growing.
  • People in the tucatinib group lived 4.5 months longer than people in the placebo group.

People who received tucatinib had more diarrhea and more cases of hand-foot syndrome than those who did not. Most of these cases could be managed.

Breakthrough therapy designation will allow tucatinib to move through the approval process more quickly, giving people access to it sooner if it is approved. The process will still take months. Tucatinib’s maker, Seattle Genetics, already submitted a New Drug Application to the FDA and hope to hear back quickly.

Tucatinib is currently being tested in another phase III trial in combination with ado-trastuzumab emtansine, which is still recruiting.

What This Means for You

The FDA’s breakthrough therapy and accelerated approval programs are designed to move promising new treatments for serious conditions through more quickly. These announcements highlight the importance of the results presented in San Antonio and the need for more options after early lines of treatment in metastatic HER2-positive breast cancer.

The approval of treastuzumab deruxtecan and the recognition of tucatinib in the hopes of a quick approval are good news for people who have few treatment options and poor outcomes after cancer has progressed on existing HER2-targeted therapies. These medicines have both shown good results after treatment with trastuzumab, pertuzumab, and ado-trastuzumab emtansine, providing important options if the cancer has progressed through two or more lines of treatment.

Tucatinib and trastuzumab deruxtecan are also being studied in other combinations and lines of treatment. If you are interested in these or other new treatment options, ask your doctor about participating in clinical trials, where you may have the chance to get a treatment before it is made widely available.