CDK4/6 inhibitors have arrived to treat hormone receptor (HR) positive, HER2 negative breast cancer, allowing innovative targeted therapies for premenopausal patients who have had very limited treatment options.
Paying more attention to detailed treatment strategies for premenopausal patients, physicians are actively discussing selective ovarian function suppression (ovariotomy) or pharmacological treatment (gonadotropin-releasing hormone agonist, GnRHa) for the use of CDK4/6 inhibitors.
Korea Biomedical Review has met with Suh Young-jin, head of the Breast Thyroid Gland Cancer Center at the Catholic University of Korea St. Vincent’s Hospital, to learn about the latest treatment strategy using CDK4/6 inhibitors in premenopausal or transitional to menopause HR+/HER2- breast cancer patients.
Question: What are the disease characteristics of local HR+/HER2- breast cancer patients, and among them, how much premenopausal patients account for?
Answer: In Korea, breast cancer is the most common cancer in women, and the incidence is increasing. HR+/HER2- breast cancer takes up about two-thirds of the total. In terms of menopause, premenopausal patients account for about one-third to half of all breast cancer patients.
In general, we explain to patients that HR+ cases have a better prognosis than those with the negative. But breast cancer has a very long survival period, unlike other cancers. So even if the disease is well managed through adjuvant therapy after surgery, a few can still have problems. If premenopausal HR+ patients come to menopause, doctors must explain to patients that they should change medications accordingly.
Q: With the arrival of CDK4/6 inhibitors in Korea and the reimbursement, the treatment environment for HR+/HER2- breast cancer patients seems to have changed a lot. What do you think?
A: The emergence of CDK4/6 inhibitors is tremendously significant. Since 2000, many anticancer drugs have been introduced. However, stage-four patients or those who have previously been treated received similar treatments. Before CKD4/6 inhibitors, there were few options other than chemotherapy. Oral drugs were mostly used for those without metastasis and no relapse after surgery. If cancer came back, they had no other method than chemotherapy. But a systemic treatment using chemotherapy caused many problems such as hair loss and isolation from daily life.
Now, it is very fortunate that a new, powerful, and effective treatment has arrived. The emergence of CDK4/6 inhibitors is especially meaningful because patients can endure therapies well and carry out daily life simultaneously. Also, their treatment outcomes are excellent, which allows maintaining treatment for a long time. This is a tremendous change not only for patients and caregivers but physicians.
Q: CDK4/6 inhibitors are innovative, but to use them in premenopausal patients, physicians should either remove ovaries or suppress ovarian function by using GnRHa, right?
A: Yes. Surgically removing the ovaries and suppressing ovarian function as much as possible share a common goal. The history of metastatic breast cancer treatment shows that a medical paper was published in the U.K. before 1900 that ovariectomy relieved the metastatic state of breast cancer. The results of a clinical trial recently announced at the American Society of Clinical Oncology meeting were consistent with the paper.
People even say physicians can make her in a postmenopausal status through artificial or medical treatment and then treat her if the patient is premenopausal.
If patients have a risk of metastasis or recurrence, it is crucial to suppress ovarian function from the start of treatment. If the ovarian function is unstably blocked, the ovaries may secrete more female hormones due to the “rebound phenomenon.”
Q: Locally available CDK4/6 inhibitors show differences in therapeutic effects and safety profiles. What are your criteria for choosing the drug?
A: The three CDK4/6 inhibitors in Korea have different safety profiles depending on their mechanisms. Verzenio (ingredient: abemaciclib) has some reports of severe gastrointestinal adverse reactions, and Ibrance (palbociclib) and Kisqali (ribociclib) reported a bit more hematologic toxicity such as neutropenia.
I am very conservative when choosing drugs. Drugs that were developed first and have been used by patients of various races and ages worldwide have many reports of effects and adverse reactions, so I prefer them. Among the three, I prefer using Ibrance because it has been used for Koreans for a long time, and it is safer with confirmed various adverse reactions.
Ibrance showed hematologic toxicity in some patients, but it did not necessarily appear intensively in senior patients, as reported in clinical studies. It differed depending on the individual patient’s condition and characteristics. Some patients had leukopenia requiring treatment despite their young age, while those in their 70s and 80s received Ibrance treatment without a problem. In a clinical trial of Ibrance, the drug did not increase Grade 3 or higher myelosuppression with age.
Q: What should be improved in breast cancer treatment?
A: In Korea, doctors do not have much autonomy to choose the drug because of the strict reimbursement criteria. Suppose a drug’s efficacy has been proved in an investigator-initiated study. In that case, the authorities should allow experts to reach a consensus and flexibly approve reimbursement for the medicine without a drugmaker’s clinical trial.
If patients fail CDK4/6 inhibitor therapy, most of them switch to chemotherapy because CDK4/6 inhibitors are not reimbursable after the treatment failure. Using chemotherapy means more severe and diverse adverse reactions, more frequent hospitalization, and longer hospital stay. We need a comparative study on how the nation’s health spending could change if the reimbursement changes flexibly depending on side effects and additional costs.