Potential New Treatment For Younger Patients with HR+, HER2- Breast Cancer
- Metastatic hormone receptor-positive, HER2-negative breast cancers are hard to treat, especially in younger patients.
- There is a need for new, more effective treatments for these cancers.
- Kisqali is CDK4/6 drug, which inhibit cyclin-dependent kinases, proteins that play a role in control cancer cell proliferation.
- Compared to traditional chemotherapy, Kisqali in combination with endocrine therapy (Kisqali/ET) is effective in delaying the progression of breast cancer. Endocrine therapy blocks hormones that feed cancer cells.
- Women receiving Kisqali/ET respond to their treatment for longer periods of time than those receiving chemotherapy.
A cancer is deemed metastatic when it has spread beyond the breast. It can involve many other organs (visceral metastases), such as the lungs or the intestines, compromising their normal function. Younger patients tend to have more aggressive disease that responds poorly to traditional chemotherapy treatments. These patients tend to have a higher level of hormones, estrogen and progesterone, which can fuel their hormone-sensitive cancers (HR+). If their cancers are additionally HER2-, they cannot be treated with highly effective drugs, such as Herceptin.
Read MoreBreast Cancer And Its Treatment
Breast cancer is an extremely common diagnosis. An average woman has a 13% or about 1 in 8 chance of developing this cancer. In 2022, around 290,000 new cases of breast cancer will be diagnosed in women, resulting in more than 40,000 deaths. This makes it the second leading cause of cancer-related death among females in the US. While the rates of breast cancer have increased by 0.5% over the recent years, the rates of death caused by this cancer have steadily decreased. This is likely because of better screening and improved therapeutics. Better treatments make it possible for even metastatic patients to live for many years, a feat that was not possible in even the recent past.RELATED: Living With Breast Cancer
These new treatments include targeted therapies, which identify and exploit specific characteristics of cancer, such as Enhertu, an antibody-drug conjugate that can benefit patients with HER2-positive or HER2-low cancers. They also include immune checkpoint inhibitors, which are drugs that remove the brakes on the immune system allowing it to attack and eliminate cancer cells. Cancer cells otherwise have surreptitious mechanisms to circumvent detection and destruction by the immune system. Another target for modern drugs is cyclin-dependent kinases (CDKs), proteins that play a crucial role in promoting the growth of cancer cells. Their action can be blocked by CDK inhibitors, of which Kisqali is one.
How Does Kisqali Work? Why Is It Paired With Endocrine Therapy?
Cancer cells divide and grow by repeatedly going through a series of proliferation events called the "cell cycle." This cycle is highly complex and regulated, meaning that several proteins within the tumor cells must be activated in a specific way at specific times for the cells to proliferate. CDKs, including CDK4/6, are just such proteins. They control key events in the cell cycle pathway, which makes them great targets for anti-cancer drugs, such as CDK inhibitors like Kisqali.
RELATED: Hormone Therapies for Breast Cancer: CDK 4/6 Inhibitors
Kisqali, however, cannot work alone. Cancer cells also have other proteins that control their growth. In response to CDKs being blocked, they can rev up the production of these other proteins to compensate for the CDK inhibition. This can effectively render CDK inhibitors useless. One way to counteract this is to inhibit such compensatory pathways as well. Thus, Kisqali can be paired with endocrine therapies, another class of drugs used to treat breast cancer.
Endocrine therapy blocks hormones, such as estrogen and progesterone. These hormones can interact with certain proteins present on the surface (estrogen receptor (ER); progesterone receptor (PR)) of breast cancer cells and fuel their growth. Such cancers are termed hormone-receptor-positive (HR+) cancers. When these cancers are starved of hormones, they are not able to continue growing.
RELATED: What is Tamoxifen for Breast Cancer?
By pairing Kisqali and ET, clinicians can launch a multi-pronged attack that cannot be easily compensated by breast cancer cells.
The Trial
RIGHT Choice is a phase II clinical trial. This phase of clinical trial tests whether a new treatment combination has the intended therapeutic effect or not.
The trial enrolled a total of 222 patients with metastatic breast cancers with aggressive features (HR+ but HER2-). More than 50% of these patients were extremely symptomatic due to tumor spread to their internal organs. Most notably, these women were either still menstruating or actively going through menopause. They were randomly assigned to receive one of two treatments: Kisqali in combination with ET or traditional chemotherapy. 112 women received the former combination, and 110 received the latter.
Trial investigators measured progression-free survival (PFS) and time to treatment failure (TTF) in these patients. PFS represents the time a patient is alive without a worsening of their disease. TTF is the length of time between treatment initiation and discontinuation for any reason, including the progression of the disease or an inability of patients to tolerate the treatment.
Women who were treated with Kisqali and ET had a PFS of 24 months, which is almost one year longer than the PFS (12.3) observed for women who received chemotherapy. TTF was also significantly improved with the Kisqali/ET combination (18.6 months). Women who received chemotherapy had a TTF of 8.5 months.
Women treated with the Kisqali/ET combination tolerated the treatment better than those treated with chemotherapy. Only 1.8% of the former patients reported significant side effects. With the latter, side effects were noted in 8% of the women. In fact, 23% of the patients receiving chemotherapy discontinued treatment due to side effects, but only 7.1% of patients receiving Kisqali/ET did so.
Side Effects
While the Kisqali/ET treatment is generally well tolerated, it is not free of side effects.
Kisqali was most commonly associated with nausea, vomiting, fatigue, diarrhea, and headaches. However, serious side effects can also occur. These include lung inflammation that may lead to trouble breathing or cough. Severe skin reactions may also occur, which can cause patients to experience a rash, burning sensation, blisters, or skin peeling. Abnormal heart rhythms, liver problems, and a drop in blood cell counts have also been reported. Rarely, these serious side effects can lead to death.
ET therapy can cause hot flashes, night sweats, vaginal dryness, loss of sex drive, mood swings, joint pains, brittle bones when used long term, and headaches.
Most of these side effects can be managed by physicians.
Is Kisqali/ET Available To Patients
Kisqali in combination with endocrine therapy is approved by the U.S. Food and Drug Administration. This combination can be used as the treatment of choice instead of chemotherapy for ER+/HER2- metastatic breast cancer patients.
Learn more about SurvivorNet's rigorous medical review process.
