The taxane can then be stopped. Trastuzumab and pertuzumab continue, and oncologists add tucatinib as a pill taken twice daily.

Dr. Sarah Poland, a breast medical oncologist and assistant professor of hematology and oncology at the University of Chicago, says oncologists will need to balance the possibility of longer cancer control against added toxicity, “particularly diarrhea and changes in liver function.”

What Does Maintenance Treatment Mean?

Induction treatment is the first, more intensive phase used to bring the cancer under control. Maintenance treatment follows when the cancer responds or remains stable. Its purpose is to preserve that control while avoiding indefinite treatment with conventional chemotherapy.

Maintenance does not mean the cancer has been cured or that treatment has ended. Metastatic breast cancer can be controlled for extended periods, but treatment generally continues until the cancer worsens or side effects become unacceptable.

HER2-positive cancers make too much of a protein called human epidermal growth factor receptor 2. That protein sends signals encouraging cancer cells to grow.

Trastuzumab and pertuzumab are antibodies that attach to different areas on the outside of HER2. Tucatinib is a targeted drug that blocks HER2 signaling inside the cell.

Together, the three target the same cancer-driving pathway in complementary ways.

Eight More Months Without Cancer Progression

The approval was based on HER2CLIMB-05, a phase 3 trial involving 654 adults. All had completed induction treatment without evidence that their cancer was worsening. Patients with no brain metastases, or with asymptomatic brain metastases, could participate.

Everyone continued trastuzumab and pertuzumab. Half also received tucatinib, while the other half received a placebo.

Median progression-free survival was 24.9 months with tucatinib and 16.3 months with placebo.

The hazard ratio was 0.64, corresponding to a 36% lower risk of progression or death during the study.

That does not mean every patient will receive exactly 8.6 additional months of control, nor does it mean patients live 36% longer. Overall-survival data were not mature when the FDA reviewed the trial, so it is not yet known whether adding tucatinib helps patients live longer.

“The HER2CLIMB-05 trial showed that patients receiving tucatinib plus HP [trastuzumab and pertuzumab] went a median of 8.6 months longer without growth or spread of their cancer compared with those receiving HP alone,” Dr. Poland told SurvivorNet.

“This new combination offers patients a more intensive maintenance option, with the potential for longer cancer control without continued chemotherapy,” she said.

Liver Toxicity Requires Close Monitoring

The updated tucatinib label contains the FDA’s strongest safety alert, a boxed warning, for severe and potentially fatal liver toxicity.

In HER2CLIMB-05, five patients developed a pattern of liver injury known as Hy’s Law, which can signal a risk of serious drug-induced liver damage. One patient died. The five cases occurred after tucatinib was restarted following an earlier liver problem.

Doctors should check liver enzymes and bilirubin before treatment, every two weeks during the first two months, and every three weeks afterward. Doctors may need to pause, reduce, or permanently stop tucatinib if the results become abnormal.

Patients should contact their cancer team promptly if they develop yellowing of the skin or eyes, dark urine, pain in the upper right abdomen, unusual nausea, loss of appetite, severe fatigue, or itching.

Diarrhea is another frequent concern. It occurred in 73% of patients treated with tucatinib, although most cases were mild or moderate. Six percent developed grade 3 diarrhea. Persistent diarrhea can lead to dehydration, low blood pressure, and kidney injury.

Trastuzumab and pertuzumab carry their own risks, including heart muscle weakening, infusion reactions, and diarrhea. Heart function generally needs monitoring during treatment.

Questions to Ask Your Doctor

• Did my cancer remain controlled during induction treatment, making me eligible for this regimen?
• How much benefit might tucatinib add in my specific situation?
• Do my liver history, medications, or alcohol use increase my risk of liver injury?
• How frequently will my liver tests and heart function be checked?
• What should I do if I develop diarrhea or symptoms of a liver problem?
• If I must stop tucatinib, can I continue trastuzumab and pertuzumab?

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