‘Practice-Changing’: FDA Approves Ibrance Combination as New Maintenance Option for HR+/HER2+ Metastatic Breast Cancer

The new treatment combines three medicines that work together to attack the cancer from multiple directions at once:

• Palbociclib (brand name: Ibrance) is a pill that helps slow cancer growth by blocking signals that tell cancer cells to divide.
• Trastuzumab (brand name: Herceptin) targets and attacks a specific protein on cancer cells called HER2.
• Endocrine (or hormonal) therapy lowers or blocks the estrogen and progesterone hormones that fuel this type of cancer’s growth.

Some patients may also receive pertuzumab (brand name: Perjeta), a second HER2-targeting medicine that works alongside Herceptin to more fully block those cancer-driving signals.

It is intended for patients whose disease has not progressed following initial chemotherapy and HER2-directed treatment. It’s important to note that investigators leading the trial excluded patients who progressed during induction chemotherapy, which likely introduces selection bias toward patients with favorable disease biology.

Hormone-receptor positive (HR+) means the cancer cells use estrogen and/or progesterone signals to grow.

Advanced or metastatic indicates the cancer has spread beyond the breast and nearby lymph nodes. This stage is generally not curable, but it often responds to medicines that block estrogen signaling or cell-cycle machinery.

The Data Behind the Approval

The approval was supported by the PATINA trial (NCT02947685), a randomized, open-label study of 518 patients with HR+/HER2+ locally advanced or metastatic breast cancer who showed no disease progression after induction treatment with a taxane (a type of chemotherapy) and trastuzumab, with or without pertuzumab.

Patients continued treatment until disease progression or unacceptable side effects.

The trial’s main goal was to measure progression-free survival (PFS), which is the amount of time a patient lives without their cancer getting worse after starting treatment. The study also evaluated overall survival (OS), which is the length of time patients remain alive after starting treatment.

Results showed a statistically significant improvement in PFS for patients who had palbociclib (Ibrance) added to their treatment plans, with or without pertuzumab.

According to the New England Journal of Medicine, “patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group, with a median duration of 44.3 months vs. 29.1 months.”

Overall survival data were also not yet mature, meaning the trial had not accumulated enough events to draw final OS conclusions.

Dr. Francisco Esteva, Chief of Hematology & Medical Oncology at Northwell’s Lenox Hill Hospital, tells SurvivorNet that understanding both the promise and the limitations of the data are important

“This is an important advance because CDK4/6 inhibition has been established mainly in hormone receptor-positive, HER2-negative breast cancer, and this approval extends that strategy to a carefully selected HER2-positive metastatic setting; however, it should be discussed with appropriate patients because overall survival data are not yet mature, and palbociclib requires monitoring for side effects, especially neutropenia,” Dr. Esteva says.

Neutropenia is when a patient has low levels or a bacteria-fighting white blood cell. Although reported cases of the condition, a complication stemming from chemotherapy, were rare, infection of any grade was more frequent in the palbociclib group (64% vs. 43%).

The recommended palbociclib dose is 125 mg taken orally once daily for 21 consecutive days, followed by seven days off for a 28-day cycle.

What This Approval Means for Patients

Dr. Sudarsan Kollimuttathuillam, a medical oncologist at City of Hope Orange County in Irvine, California, says the approval addresses a meaningful gap in the treatment continuum.

Adding palbociclib to HER2-directed and endocrine therapy “potentially gives some patients more time on an effective treatment before needing to move to the next line of care. For this subtype of metastatic breast cancer, this approval offers another meaningful option to help keep the disease controlled longer,” he tells SurvivorNet.

Dr. Reid echoes that significance.

“These findings establish a new standard-of-care maintenance strategy that leverages dual hormone receptor and HER2 pathway targeting to prolong disease control for patients with HR+/HER2+ metastatic breast cancer,” she says

Potential Side Effects

According to the palbociclib manufacturer, Pfizer, patients in the PATINA trial experienced a range of side effects, with those in the palbociclib group experiencing more blood cell-related issues.

Decreases in white blood cell counts occurred in 94% of patients receiving palbociclib, compared with 25% in the control group. Decreased neutrophil counts (a type of white blood cell critical to fighting infection) were seen in 93% vs. 19%, reduced hemoglobin (a marker of anemia) in 81% vs. 47%, and lowered platelet counts in 59% vs. 6%.

Infections were also more common in the palbociclib group (64% vs. 43%), consistent with the immune-suppressing effect of reduced white blood cell counts.

Gastrointestinal effects, including diarrhea, mouth sores (stomatitis), and nausea, were also documented.

What is HER2+ Breast Cancer?

HER2 stands for human epidermal growth factor receptor 2. It’s a protein that helps breast cancer cells grow quickly.

Traditionally, the presence of HER2 has been divided into two groups: either positive or negative. These groupings are based on how the tumors appear under a microscope when graded by the pathologist, or on additional testing a pathologist may perform.

HER2-positive means the tumor shows HER2 overexpression, while patients with HER2-negative tumors show minimal or no expression.

Patients who have a minimal amount of HER2 expression but do not meet the classic definition for HER2-positive tumors are considered to be HER2 “low.”

WATCH: The Unique Features of Breast Cancer

What Is HR+ Breast Cancer?

Hormone receptors are proteins found on breast cells. They pick up the estrogen or progesterone signals that promote cell growth, including cancer cell growth, if they contain the receptors for those hormones.

Breast cancer cells that have receptors for either hormone are considered hormone receptor-positive (HR+).

Breast tumors may be positive for estrogen receptors (ER+), progesterone receptors (PR+), or both (ER/PR+). About 80% of all breast cancers are ER-positive, and more than half of those are also PR-positive (ER/PR+).

If a cancer cell is ER+, it means it can receive signals from estrogen, instructing the cells to grow. If a cancer cell is PR+, these signals can come from the progesterone hormone.

Knowing whether the tumor needs estrogen and/or progesterone to grow makes it easier to treat the cancer.

Breast cancer cells can test positive for hormone receptors across different stages of the disease. However, hormone receptor status is closely tied to breast cancer subtype. For example, triple-negative breast cancer is defined by the absence of these receptors.

Metastatic Breast Cancer

Stage 4 breast cancer means that your cancer has now spread to distant areas of the body. It is no longer localized to the breast or nearby lymph nodes — instead, it has spread to distant organs such as the bones, liver, lungs, or brain.

WATCH: Understanding Stage 4 Breast Cancer

While there is no cure for metastatic breast cancer, doctors have a lot of options to treat this stage of advanced disease. One advantage of being such a common cancer is that breast cancer has been the focus of much research.

What scientists have learned in the lab has translated into new and breakthrough treatments that are dramatically improving the outlook for people with this cancer.

So, if you have been diagnosed, your doctor will work with you to identify the treatment options best suited to your specific cancer and circumstances.

To further help you on your cancer journey, explore SurvivorNet’s proprietary AI tool, “My Health Questions.”

WATCH: How One Cancer Survivor and Her Sister Used “My Health Questions” to Navigate Care

This powerful resource, embedded across the SurvivorNet website, was built to bridge that gap by offering on-demand explanations of treatment options, clinical trials, side effects, insurance concerns, and more.

Questions To Ask Your Doctor

• Is my breast cancer HR+, HER2+, or both?
• Is the treatment combination using palbociclib (Ibrance) an option for me?
• What side effects should I be aware of?
• Are there other options I might tolerate better?

Learn more about SurvivorNet's rigorous medical review process.

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