Addition of palbociclib improves outcomes in HER2-positive, hormone receptor-positive metastatic breast cancer | SABCS 2024

People who took palbociclib (Ibrance) in addition to HER2-targeted and hormonal therapies experienced an average of 15 months longer without cancer growth or spread than those who received only HER2-targeted and hormonal therapies.

Background

HER2 is a protein found at high levels in 15-20% of breast cancers, roughly half of which are also hormone receptor-positive. Since doctors first identified HER2 as a driver of some breast cancers, they have developed multiple drugs that target the protein. Right now, eight anti-HER2 drugs are approved for use in breast cancer in the United States.

Treatment for HER2-positive breast cancer focuses heavily on these drugs. They can be effective for early-stage disease. Once the cancer spreads, the drugs are less consistent and sometimes stop working, making the cancer hard to treat.

CDK 4/6 inhibitors are a newer class of breast cancer drugs. Three approved drugs in this class—including palbociclib—are often combined with hormonal therapy to treat hormone receptor-positive breast cancers. Early research has shown a potential benefit to combining CDK 4/6 inhibitors and anti-HER2 medicines.

Results

In a randomized control phase III trial called PATINA, adding palbociclib to standard treatment helped delay cancer growth or spread by 26% in people with HER2-positive, hormone receptor-positive metastatic breast cancer. The people receiving palbociclib went an average of 44.3 months without cancer growth compared to 29.1 months in the standard treatment group.

As the study team continues to follow participants, the benefit remains strong, although it is too soon to see results for overall survival.

The PATINA trial included 518 people with HER2-positive, hormone receptor-positive metastatic breast cancer. Participants in the control group received the standard treatment of anti-HER2 therapy plus hormonal therapy. The study group received the standard treatment plus palbociclib, a CDK 4/6 targeted therapy. The anti-HER2 therapy was trastuzumab plus or minus pertuzumab. The hormonal therapy was fulvestrant or an aromatase inhibitor.

Participants were mostly white (91%) women with an average age of 53. They had undergone, on average, six cycles of induction chemotherapy before entering the trial. Induction chemotherapy is given before the primary drug therapy, similar to the way neo-adjuvant chemotherapy may be given before surgery.

One-fifth of the people in the trial were trying anti-HER2 therapy for metastatic breast cancer for the first time, in most cases because they had de novo disease (metastatic at first diagnosis) that had already spread at the time of diagnosis.

While the drug combination was generally well tolerated, people in the palbociclib group were more likely to experience neutropenia, fatigue, diarrhea, and stomatitis than people in the control group. These side effects are typical of this medicine.

It is worth noting that people in both PATINA trial groups had better outcomes than those in previous standard treatment studies. Those studies include CLEOPATRA, the trial that led to the 2012 FDA approval of pertuzumab as a first treatment for HER2-positive breast cancer. This difference is likely due to a difference in study population. To be eligible for the PATINA study, patients had to show no evidence of disease after induction chemotherapy. People whose cancers were resistant to therapy from the start could not join the trial.

What does this mean for you?

These results are potentially exciting for people with HER2-positive, hormone receptor-positive metastatic breast cancer for two reasons:

• First, the results mean that a new treatment option may be available soon. The study author suggested that adding palbociclib may become part of standard practice but did not provide a timeline.
• Second, this study opens the door to other possible lines of research. The drug combination tested in this trial blocks two areas of activity in cancer cells. The study author said that most HER2-positive breast cancer treatment has focused on HER2 and paid less attention to other biomarkers, aside from hormone status.

LBBC medical advisory board member Sara Hurvitz, MD of Fred Hutchinson Cancer Center, commented on the study. Dr. Hurvitz sees the medical community as moving away from a one-size-fits-all approach to HER2-positive breast cancer and towards more personalized treatment.

If you are interested in learning more, talk with your doctor about this study and whether it might change their recommendations for you.