Major Advancement for HR+, HER2- Breast Cancer
- Men and women with early-stage HR+, HER2- breast cancer that has a high or medium risk of returning after surgery may have hope in preventing it from coming back.
- According to a new study, ribociclib (brand name Kisqali) plus endocrine therapy after surgery reduced the risk of invasive tumor recurrence by 25%.
- The data is being presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, the largest cancer convention in the world.
- HR+, HER2- breast cancer is the most common subtype of breast cancer.
- While these patients may be eager to move on from treatment after surgery, it’s important for them to talk with their doctor about what options are available to prevent the cancer from returning.
According to a new study, ribociclib (brand name Kisqali) plus endocrine therapy after surgery reduced the risk of invasive tumor recurrence by 25% in patients with early-stage breast cancer that was hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) and had a high or intermediate risk of recurrence.Read More
Plus, about half of early-stage HR+ breast cancers stop responding to hormone therapy.
Dr. Eleonora Teplinsky, head of Breast Medical Oncology at Valley Health System, told SurvivorNet that patients should speak to their doctors about this potential treatment option to understand risks vs. benefits.
“I really believe in making patients partners in their healthcare and having them be their own health advocates,” Dr. Teplinksky said.
“So I think it’s really important to say, look, we have this new medication, here are the benefits, here are the side effects and then work with each individual patient [to decide] whether it’s something that is going to be right for them.”
Expert Information on CDK4/6 Inhibitors
Kisqali is part of a class of drugs called CDK4/6 inhibitors, which work to interrupt the growth of cancer cells. It’s currently only approved for HR+, HER2- breast cancer that is metastatic (has spread), and it’s been a game-changer.
But this suggests there is an effective option for these earlier-stage patients, potentially opening the door for a wider range of patients to benefit.
Meanwhile, Kisqali even showed to be effective for patients whose cancer hadn’t even spread to the lymph nodes yet. The drug cut the risk of recurrence by 37% in this subgroup. However, it’s important to note that the showing wasn't statistically significant.
“While a number of patients are still on treatment, given the statistically significant and clinically meaningful improvement in disease-free survival, along with the trend in overall survival, the results have implications to change practice,” Dr. Aditya Bardia, director of the breast cancer research program at Mass General Cancer Center, told SurvivorNet.
Dr. Bardia is also a co-author on the study.
After early-stage HR+, HER2- patients have their cancer surgically removed, they may be eager to move on from treatment and get back to normal life, which is understandable. But if there is a high or medium risk of the cancer returning, it may be beneficial for them to talk with their doctor about what options are available to prevent that from happening.
The data, from the NATALEE clinical trial, is being presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, the largest cancer convention in the world.
WATCH: Understanding a New Breast Cancer Diagnosis
HR+ Breast Cancer
Hormone receptors are proteins found on breast cells that pick up either estrogen or progesterone signals and promote cell growth. If the cancer has one of those receptors, meaning it is hormone receptor-positive (HR+), the hormones help the cancer to grow.
Breast tumors may be positive for estrogen receptors (ER+), progesterone receptors (PR+) or both (ER/PR+). About 80% of all HR+ breast cancers are ER+ or ER/PR+, according to Penn Medicine.
What Is HER2 in Breast Cancer?
HER2 stands for human epidermal growth factor receptor 2. It's a protein that can be found on the surface of breast cancer cells ad make them grow quickly.
Tumors can be HER-negative, meaning they show minimal or no expression of the protein.
Tumors can also be HER2-low or HER2-positive, depending on the level of the protein present. They respond well to treatments that target the HER2 protein, such as Enhrtu (trastuzumab deruxtecan) or Herceptin (trastuzumab).
What's the New Data?
The NATALEE phase III clinical trial was a randomized phase III trial that included more than 5,000 men and women recruited between January 2019 and April 2021.
A phase III trial offers the highest level of evidence for the benefit of a new treatment.
- All patients included in the study had early-stage breast cancer, meaning they had a small tumor in the breast without spreading to other organs (stage IIA, stage IIB, or stage III, per AJCC)
- All patients had HR+, HER2- breast cancer.
After surgery, patients were randomized into two groups: 2,549 patients received ribociclib and endocrine therapy after surgery, while 2,552 patients received only endocrine therapy after surgery.
The study demonstrated that adding ribociclib to endocrine therapy after surgery reduced the risk of invasive tumor recurrence by 25% in patients. At three years, about 90.4% of ribociclib takers had no recurrence, versus 87.1% for control group.
“These landmark results will fundamentally change how we treat patients with stage II and III HR+/HER2- early breast cancer who are in need of new, well-tolerated options that prevent their cancer from coming back,” Dr. Dennis Slamon, Director of Clinical/Translational Research at UCLA Jonsson Comprehensive Cancer Center and lead author, said in a press release.
How Does Kisqali Work?
Ribociclib is a CDK4/6 inhibitor, which helps slow down the growth of cancer in women with HR+, HER2- breast cancer.
CDK4/CDK6 inhibitors are targeted therapies that attack proteins known as the cyclin-dependent kinases 4 and 6 (CDK4/CDK6).
These proteins control how quickly cells divide and multiply, and for women with breast cancer, these proteins can cause cancer cells to grow uncontrollably. That's where CDK4/CDK6 inhibitors come in they slow down or stop the proteins from multiplying.
WATCH: CDK4/6 Inhibitors for Breast Cancer, Explained
There are three drugs within this class that are approved:
- Abemaciclib (brand name Verzenio), approved for HR+, HER2- breast cancer that is advanced or metastatic, or that is early stage and is node-positive with a high risk of recurrence
- Palbociclib (brand name Ibrance), approved for HR+, HER2- breast cancer that is advanced or metastatic
- Ribociclib (Kisqali)
While these drugs are generally well tolerated by patients, they can come with unpleasant side effects patients should be aware of.
What are the Side Effects?
Dr. Teplinsky helped SurvivorNet understand some of the potential side effects of Kisqali, stressing that patients should discuss them with their doctors before beginning treatment.
She said some of the most common symptoms include:
- Low white blood cell counts, such as neutropenia (which can cause fever, chills, cough and more)
- Hair thinning
“The side effects look different in every single person,” Dr. Teplinsky said. “So it’s sometimes hard to know how someone will tolerate the medication until we put them on it.”
She indicated that it’s important for patients to understand that they could be on Kisqali for years, which means they could experience a symptom like diarrhea for an extended period. Dr. Teplinsky said patients should take this into consideration with their doctor when deciding together if the drug’s benefits outweigh risks.
For example, the negative side effects may be outweighed by the benefit for a patient who has a high risk of the cancer returning.
However, “I think it’s a really hard decision for someone whose risk is a little bit lower to begin with,” she said.
“How you navigate that is really going to be an individual conversation between patient and doctor and balancing all of those side effects with the benefit,” Dr. Teplinsky said.
And if you do experience symptoms, talk with your doctor, because they can help you find ways to manage them and have a better quality of life while taking the drug.
Questions to Ask Your Doctor
It’s important for patients to know that if they have a higher chance of their early-stage HR+, HER2- breast cancer returning after surgery, there may be options available to prevent that from happening.
It’s key to talk with your healthcare team about your eligibility for CDK4/6 inhibitors and if they may be able to help you.
Here are some questions you may consider asking your doctor to help get the conversation started:
- Does my breast cancer have a higher chance of returning?
- Would a CDK4/6 inhibitor help prevent it from coming back?
- Am I eligible to receive Kisqali?
- How do I know my hormone receptor or HER2 status?
- How will I feel during treatment?
- What are the most common side effects of Kisqali?
- Are there ways to manage the side effects?
- What will my treatment cost? Will my treatment be covered by my medical insurance company?
- Is financial assistance available or are there other organizations that can help me?