Study: CDK inhibitors may increase survival for ER-positive metastatic breast cancer patients
Contents
At a glance | Questions for your doctor |
Findings | In-depth |
Clinical trials | Limitations |
Guidelines | Resources |
STUDY AT A GLANCE
This study is about:
Whether adding a drug known as a CDK4/6 kinase inhibitor (a drug that stops cancer cells from multiplying) added to hormonal therapy improves survival in young women with , hormone positive breast cancer.
Why is this study important?
This is the first large clinical trial to look exclusively at the effect of a CDK4/6 inhibitor on overall survival in pre- or perimenopausal women with , , hormone receptor-positive breast cancer. This report follows up earlier results indicating that a CDK4/6 inhibitor lengthened progression free survival.
Study findings:
The study looked at 672 premenopausal or perimenopausal patients with , hormone receptor positive breast cancer. All patients received hormonal therapy. Participants were randomly selected to receive the CDK4/6 inhibitor ribociclib (Kisqali) or a .
The primary endpoint of this trial was progression-free survival (PFS). Results were reported in 2018.
- Median progression-free survival (PFS) was 24 months in the ribociclib group compared with 13 months in the group.
The secondary endpoint, overall survival, was reported at the 2019 American Society of Clinical Oncology Meeting.
- Ribociclib plus endocrine therapy resulted in a statistically significant longer overall survival than endocrine therapy alone.
- Estimated overall survival at 42 months was 70.2% in the ribociclib group and 46.0% in the group.
- The risk of death was 29% lower in the ribociclib arm.
The most common reported in both groups was a low white blood cell count, also known as neutropenia.
- 63% of patients who received ribociclib had neutropenia compared to 5% of patients who received a .
- 11% of patients who received ribociclib had liver, gallbladder, bile ducts or bile compared to 7% of patients who received a .
- 2% of patients who received ribociclib had an abnormal heartbeat compared to 1% of patients who received a .
What does this mean for me?
This is the first study to show that ribociclib plus hormone therapy improved overall survival compared with plus hormonal therapy in premenopausal women with , advanced breast cancer. This study confirms that there is benefit for this drug combination in these patients.
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Posted 7/22/19
Note: On 09/13/19 the issued a safety alert that Ibrance (palbociclib), Kisqali (ribociclib), and Verzenio (abemaciclib) may cause a rare but severe inflammation of the lungs.
References
Tripathy D, Im SA, Colleoni M, et al. “Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.” Lancet Oncology. 2018;19 (7):904-915. doi: 10.1016/S1470-2045(18)30292-4.
Im SA, Lu YS, Bardia A, et al. “Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer.” New England Journal of Medicine. June 4, 2019. doi: 10.1056/NEJMoa1903765.
Disclosure
FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
This article is relevant for:
People with metastatic, hormone-positive, Her2-negative breast cancer
This article is also relevant for:
people with ER/PR + cancer
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IN-DEPTH REVIEW OF RESEARCH
Study background:
In MONALEESA-2, ribociclib plus the aromatase inhibitor letrozole showed improved progression-free survival compared with letrozole alone as treatment for postmenopausal patients with hormone receptor-positive, , advanced breast cancer. However, the impact on premenopausal women was not determined.
Young women with breast cancer tend to have poorer prognoses and more aggressive cancer compared to older women. Premenopausal women are underrepresented in clinical trials. MONALEESA-7 is the first Phase III trial with a CDK4/6 inhibitor exclusively in premenopausal patients. This allows researchers to more directly ask whether CDK4/6 inhibitors may benefit premenopausal women who are often also on endocrine therapy.
Researchers of this study wanted to know:
Building on the MONALEESA-2 results, the MONALEESA-7 trial aimed to assess the usefulness and safety of ribociclib plus endocrine therapy for premenopausal women with advanced, hormone receptor-positive, advanced breast cancer.
Population(s) looked at in the study:
Patients in each group of the study had similar average characteristics. The average age of the 335 participants who received ribociclib was 43 (ages ranged from 25-58). Most of these participants were white (56%) and did not have prior or endodcrine therapy (62%). Only 14% had prior chemotherapy for advanced disease. Similarly, most patients who received were white (60%) and did not have prior or endocrine therapy (48%). Identical to the ribociclib group, 14% of control patients had prior chemotherapy for advanced disease.
Study design:
A total of 672 women who had pre- or perimenopausal advanced breast cancer before the age of 59 and who had only up to one prior line of chemotherapy and had not received endocrine therapy for disease were to receive endocrine therapy with either ribociclib or . The primary endpoint was progression free survival with a secondary endpoint of overall survival.
Study findings:
- Median progression-free survival was almost 24 months in the group that took ribociclib with endocrine therapy compared to 13 months in the group that received endocrine therapy only.
- Overall survival was analyzed at a pre-specified time; 192 deaths occurred before that time.
- Ribociclib plus endocrine therapy resulted in statistically significant longer overall survival than endocrine therapy alone.
- Estimated overall survival at 42 months was 70.2% in the ribociclib group and 46.0% in the group.
- Ribociclib plus endocrine therapy resulted in statistically significant longer overall survival than endocrine therapy alone.
At the interim analysis point (median follow-up was 35 months), 35% of patients receiving ribociclib were still on the trial while only 17% of the patients who received a remained. The predominant reason for ending treatment in both groups was disease progression.
Progression-free survival 2 (PFS2) time from when individuals were to when they progressed to the next line of therapy or died differed between the two groups. Patients in the ribociclib group showed a 31% improvement in PFS2 compared to patients who received .
The time to first subsequent chemotherapy differed by treatment group. It was longer for the ribociclib group than it was for the group of patients who received . At 42 months, 66% of patient in the ribociclib group had not received chemotherapy compared to 49% of patients in the group. The most common subsequent therapies in both groups after treatment was discontinued were chemotherapy alone and endocrine therapy alone.
Grade 3 (severe) or 4 (life-threatening) adverse events reported in more than 10% of patients in either group were neutropenia (low white blood cell count), hepatobiliary (chronic liver disease), and long QT interval (erratic heatbeat). Serious adverse events occurred in 18% of patients in the ribociclib group and in 12% of patients in the group, of which 4% and 2%, respectively, were attributed to the study regimen. Adverse events lead to discontinued treatment in 4% of patients in the ribociclib group and 3% of patients in the group.
Limitations:
Few data are available from large studies of for young women with breast cancer. Because ribociclib is four times more selective for the CDK4 enzyme than CDK6 enzyme, more research is needed to determine if the effect observed in this trial was due to ribociclib or if other CDK4/6 inhibitors would be as effective.
Conclusions:
The results of the MONALEESA-7 trial show that there is substantial clinical benefit with ribociclib and endocrine therapy compared to endocrine therapy alone for young pre- or perimenopausal women with hormone receptor-positive, metastatic breast cancer.
Share your thoughts on this XRAYS article by taking our brief survey.
Posted 7/22/19
The National Comprehensive Cancer Network (NCCN) guidelines for the treatment of advanced or ER-positive breast cancer include the following:
Genetic testing
- All people diagnosed with breast cancer meet guidelines for genetic counseling and testing.
NCCN preferred treatment options
The NCCN lists the following preferred treatments for ER-positive and breast cancer:
- for people with or mutations:
- Lynparza () or () for people with an inherited or mutation.
- therapy
- A combination of hormonal therapy (aromatase inhibitor or Fulvestrant) + with a CDK4/6 inhibitor:
- abemaciclib (Verzenio), palbocicib (Ibrance) or ribociclib (Kisqali).
- A combination of hormonal therapy (aromatase inhibitor or Fulvestrant) + with a CDK4/6 inhibitor:
- For second-, third- or later lines of therapy:
- A combination of hormonal therapy (aromatase inhibitor or Fulvestrant) plus with a CDK4/6 inhibitor for people who have not previously received a CDK4/6 inhibitor.
- Enhertu (trastuzumab deruxtecan) for people with HER2-low ( 1+ or 2+) tumors, who received chemotherapy for disease and whose cancer no longer responds to hormonal therapy.
- Piqray (apelisib) for cancers that test positive for a PIK3CA mutation.
- Oserdu (elacestrant) for , cancers that test positive for an ESR1 mutation.
- Lynparza () or () for BRCA1/BRCA2 for tumors with a or mutation.
- A combination of everolimus and hormonal therapy.
- Hormonal therapy alone.
- Trodelvy (sacituzumab govitecan-hziy) for , after prior treatment, including hormone therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy (including a taxane).
Updated: 03/21/2023
- Is my cancer and ?
- Am I candidate for ribociclib plus hormonal therapy?
- As a premenopausal woman, what is the best therapy for my breast cancer?
- What are the benefits and risks of hormonal therapy?
- What are the benefits and risks of CDK4/6 inhibitor therapy?
- What are the side effects of CDK4/6 inhibitors?
The following studies look at treatment for people with ER-positive breast cancer.
- NCT04673448: Combining the Dostarlimab and Niraparib for Advanced or Breast, Ovarian or Pancreatic Cancer with an Inherited or Tumor Mutation. This study is looking at the effectiveness of combining the , and the dostarlimab for treating people with an inherited mutation (found with genetic testing) or a tumor mutation (found through tumor testing) who have advanced breast, pancreatic or ovarian cancer.
- NCT05501886: Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or HR+/HER2- Breast Cancer (VIKTORIA-1). This study is looking at the efficacy and safety of the selective receptor degrader (SERD) gedatolisib plus fulvestrant with or without palbociclib for the treatment of patients with locally advanced or HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.
- NCT04975308: A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer (EMBER-3). This study will evaluate the efficacy and safety of the selective receptor degrader (SERD) imlunestrant, how it works compared to standard hormone therapy, and how well imlunestrant with abemaciclib works compared to imlunestrant in participants with breast cancer that is ER-positive and .
- NCT05306340: A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With Exemestane Plus Everolimus in Participants With Receptor-Positive, , Locally Advanced or Breast Cancer (evERA Breast Cancer). This study will evaluate the efficacy and safety of the selective receptor degrader (SERD) giredestrant, plus everolimus compared with exemestane plus everolimus in people with receptor ER-positive, locally advanced or breast cancer who have had previous treatment with a CDK4/6 inhibitor and hormone therapy.
- NCT03344965: Expanded - Treating Breast Cancer in People without gBRCA Mutations. This study will look at whether is also effective for treating breast cancer in people who do not have an inherited mutation. The study is enrolling people with an in or an acquired (tumor) mutation in or .
- NCT03685331: , Palbociclib and Fulvestrant for BRCA-Associated, ER/PR+/HER2-Negative Breast Cancer. This study is looking at the side effects and best dose of palbociclib when given with and fulvestrant for people with HR+/HER2-negative mBC who have a or mutation.
- NCT04072952: ARV-471 Alone and in Combination With Palbociclib in Patients With ER+/HER2- Locally Advanced or Breast Cancer. This is a dose escalation and expansion study to learn the safety and tolerability of ARV-471 alone and combined with palbociclib in people with ER+/HER2- locally advanced or breast cancer who have received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.
- NCT04448886: Sacituzumab Govitecan +/- Pembrolizumab In HR+ / - MBC. This research study is evaluating the safety and effectiveness of Sacituzumab Govitecan with or without Pembrolizumab in HR+/HER2- breast cancer.
- NCT04563507: Combined Immunotherapies in ER+ Breast Cancer. Patients receiving standard therapy for HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to also receive Stereotactic Body Radiation Therapy(SBRT) to each lesion.
- NCT04895358: Pembrolizumab Plus Chemotherapy Versus Plus Chemotherapy for HR+/HER2- Inoperable or Breast Cancer (KEYNOTE-B49). The study will look at the safety and efficacy of pembrolizumab plus chemotherapy compared to chemotherapy alone in the treatment of HR+/HER2- locally recurrent inoperable or breast cancer.
Other clinical trials for people with breast cancer can be found here.
Updated: 12/22/2023
The following studies are looking at treatment for people with advanced .
- NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced .This study will test the safety and effectiveness of the experimental drug NUV-868 alone and combined with a in people with advanced . This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
- NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of ceralasertib administered orally in combination with chemotherapy regimens and/or novel anticancer agents to patients with advanced cancer. The study is enrolling people with inherited mutations, including , , , , , and people with tumors that are HRD-positive.
- NCT04644068: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (PETRA). This research is designed to learn whether treatment with a new , AZD5305, used alone or in combination with anti-cancer agents is safe, tolerable and has anti-cancer activity in patients with advanced . The study is open to people who have previously been treated with PARP inhibitors.
- NCT04267939: ATR Inhibitor Plus Study in Advanced and Ovarian Cancer. This study will look at how well people with advanced respond to treatment with the BAY1895344 in combination with the . This study is open to people with inherited mutations in , , and other genes. Contact the study coordinator for information about eligibility for people with mutations in other genes.
- NCT04657068: Treatment with ATR Inhibitor for Advanced or Solid Tumors. This study will look at how well a new oral known as an ATR inhibitor works on advanced or with mutations in genes that are linked to damage repair. This study is open to people who have an inherited or acquired or mutation or whose tumors are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
Updated: 02/01/2024
The following organizations offer peer support services for people with, or at high risk for breast cancer:
- FORCE peer support:
- Our Message Boards allow people to connect with others who share their situation. Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Connect online with our Private Facebook Group.
- Join our virtual and in-person support meetings.
- Other organizations that offer breast cancer support:
Updated: 05/07/2024
Who covered this study?
Medscape
First CDK4/6 Inhibitor to Improve Survival in Metastatic Breast Cancer This article rates 5.0 out of 5 stars
Eureka Alert
Ribociclib plus hormone therapy extends survival for patients with premenopausal advanced hormone receptor-positive breast cancer This article rates 4.0 out of 5 stars