Researchers have developed a targeted therapy that may significantly increase the survival of pre-menopausal women with advanced breast cancer, according to findings recently presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.
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In an international, randomized, phase III clinical trial, researchers added an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) to standard endocrine therapy for women with advanced HR-positive/HER2-negative breast cancer.
The researchers report that adding the CDK inhibitor significantly increased survival among the women, compared with using the endocrine therapy alone.
After a follow-up period of 42 months, the survival rate among women who received the new inhibitor was 70%, compared with just 46% among women who only received the endocrine therapy.
This is the first study to show improved survival for any targeted therapy when used with endocrine therapy as a first-line treatment for advanced breast cancer.
~ Dr. Sara Hurvitz, Lead Author
The fact that the new therapy significantly prolonged overall survival is “good news for women with this terrible disease,” she adds.
What is advanced breast cancer?
Advanced breast cancer is the leading cause of death from cancer among women age 20 to 59 years. It is less common among premenopausal women than among older women, but incidence of the cancer among this population is on the rise. In the United States, the incidence among women aged 20 to 39 years increased by 2% annually between 1978 and 2008.
The growth of some breast cancers is stimulated by the hormone estrogen, in which case the cancer is referred to as estrogen receptor positive (ER+). Around 80% of breast cancers fall into this category, in which case they are referred to as hormone-receptor positive (HR+) cancers. Cancers that are ER+ are significantly more likely to respond to hormone therapy than ER-negative cancers.
Hormone or endocrine therapy works by blocking the effect that estrogen has on breast cancer cells. The therapy is only prescribed when women have an ER+ cancer, in which case the treatment may be used to reduce tumor size prior to surgery, to reduce the risk of recurrence after surgery or to target cancer that has already recurred or spread.
Developing a new ‘first-line’ treatment for breast cancer
The therapy used in the current trial blocks the activity of cyclin-dependent kinases 4 and 6 (CDK 4/6) − enzymes that promote cancer cell proliferation. CDKs drive cell cycle progression and regulate transcription. Dysregulated CDKs commonly occur in cases of cancer, making them a popular therapeutic target in anticancer strategies.
In 2018, the current therapy was FDA-approved for use in combination with an aromatase inhibitor for the treatment of pre- and perimenopausal women with HR+, HER2-negative advanced or metastatic breast cancer.
The MONALEESA-7 trial is the first of its kind to focus specifically on premenopausal women aged under 59 years with advanced breast cancer who have not been treated with endocrine therapy before.
Participants were randomly assigned to receive either the CDK inhibitor or a placebo in combination with an injectable estrogen-suppressing endocrine therapy and either one of two aromatase inhibitors or tamoxifen (tamoxifen is a drug that inhibits the effects of estrogen on breast tissue and it has been used to treat breast cancer for more than 40 years).
A total of 672 women took part in the study. After an average follow up period of 34.6 months, 173 (26%) of the women were still taking the therapies. One hundred and sixteen (35%) were still taking the new inhibitor, while 57 (17%) were still taking the placebo.
Those who received the CDK inhibitor survived for a median of 23.8 months, without experiencing disease progression, compared with just 13 months among those who took the placebo.
After a follow-up period of 42 months, the survival rate among the group taking the CDK inhibitor was 70%, compared with 46% among those who received the placebo. This translates as a 29% relative reduction in risk for death when the new inhibitor is included in the treatment regimen.
Furthermore, among the women who took the CDK inhibitor in combination with one of the aromatase inhibitors or tamoxifen, the survival rate was 70% and 71%, respectively, compared with a rate of 43% and 55%, respectively, among the women who received placebo.
This is the first time that a CDK4/6 inhibitor or any targeted agent + ET [endocrine therapy] has demonstrated significantly longer OS [overall survival] vs ET alone as initial endocrine-based therapy.”
The researchers are now analysing patient-reported outcomes and the clinical findings, including searching for biomarkers and circulating tumor DNA that may help them establish which women may benefit the most from taking the new therapy. They are also assessing the use of the drug and endocrine therapy among both women and men with early-stage HR+, HER2-negative breast cancer.
Advanced breast cancer in pre-menopausal women can be very aggressive. It is important and encouraging to see a targeted therapy that significantly increases survival for younger women with this disease.”
~ Dr. Harold Burstein, ASCO
Phase III MONALEESA-7 trial of premenopausal patients with HR+/HER2− advanced breast cancer (ABC) treated with endocrine therapy ± ribociclib: Overall survival (OS) results. 2019. J Clin Oncol.
Adding Ribociclib to First-Line Endocrine Therapy Significantly Improves Survival for Pre-Menopausal Women With Advanced Breast Cancer. ASCO Press Release 1st June 2019.