XRAYS - Making Sense of Cancer Headlines

FORCE’s eXamining the Relevance of Articles for Young Survivors (XRAYS) program is a reliable resource for breast cancer research-related news and information. XRAYS reviews new breast cancer research, provides plain-language summaries, and rates how the media covered the topic. XRAYS is funded by the CDC.

XRAYS logo and women

CDK inhibitors may increase survival for ER-positive metastatic breast cancer patients


This research is relevant for:

Unhecked Previvors

Unhecked Men with breast cancer

Unhecked Triple negative breast cancer

Checked ER/PR +

Unhecked Her2+ breast cancer

Unhecked People with a genetic mutation linked to cancer risk

Checked Breast cancer survivors

Checked Women under 45

Checked Women over 45

Checked Metastatic cancer

Unhecked Healthy people with average cancer risk

Be a part of XRAYS

XRAYS:  Making Sense of Cancer Headlines

The phase III MONALEESA-7 study is a clinical trial looking at the effect of a type of treatment known as a CDK4/6 inhibitor in pre- or perimenopausal women with hormone receptor–positive advanced breast cancer. (7/22/19) 

 

 

5 likes

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 metastatic, 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 metastatic, Her2-negative, 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 metastatic, hormone receptor positive breast cancer. All patients received hormonal therapy. Participants were randomly selected to receive the CDK4/6 inhibitor ribociclib (Kisqali) or a placebo.

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 placebo 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 placebo group.
    • The risk of death was 29% lower in the ribociclib arm.

The most common adverse event 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 placebo.  
  • 11% of patients who received ribociclib had liver, gallbladder, bile ducts or bile toxicity compared to 7% of patients who received a placebo.
  • 2% of patients who received ribociclib had an abnormal heartbeat compared to 1% of patients who received a placebo.

What does this mean for me?

This is the first study to show that ribociclib plus hormone therapy improved overall survival compared with placebo plus hormonal therapy in premenopausal women with ER/PR-positive, HER2-negative advanced breast cancer. This study confirms that there is benefit for this drug combination in these patients.

Note: On 09/13/19 the FDA issued a safety alert that Ibrance (palbociclib), Kisqali (ribociclib), and Verzenio (abemaciclib) may cause a rare but severe inflammation of the lungs.

(back to top)

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 first-line treatment for postmenopausal patients with hormone receptor-positive, HER2-negative, 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, HER2-negative 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 neoadjuvant or adjuvant endodcrine therapy (62%).  Only 14% had prior chemotherapy for advanced disease.  Similarly, most patients who received placebo were white (60%) and did not have prior neoadjuvant or adjuvant 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 metastatic disease were randomized to receive endocrine therapy with either ribociclib or placebo. 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 placebo group.

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 placebo remained. The predominant reason for ending treatment in both groups was disease progression.

Progression-free survival 2 (PFS2) time from when individuals were randomized 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 placebo.

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 placebo. At 42 months, 66% of patient in the ribociclib group had not received chemotherapy compared to 49% of patients in the placebo 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 toxicity (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 placebo 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 placebo group.

Limitations:

Few data are available from large studies of targeted therapy 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, HER2-negative metastatic breast cancer.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted 7/22/19

Related Information and Resources

FORCE XRAYS: FDA issues warning on CDK inhibitors

FORCE Information: Metastatic Breast Cancer Portal

FORCE Information: Making the decision about clinical trials

FORCE Information: Tips for searching for treatment studies

FORCE’s Research Study Search Tool

FORCE XRAYS category: Metastatic breast cancer

Breastcancertrials.org

FORCE XRAYS: The impact of palbociclib (Ibrance) on overall survival for metastatic breast cancer patients in the PALOMA-3 trial

FORCE XRAYS Category: Metastatic Breast Cancer

METAvivor is a non-profit organization dedicated to increasing awareness of advanced breast cancer and equity in research and patient support.

Metastatic Breast Cancer Alliance aims to improve the lives and outcomes for those living with metastatic breast cancer and their families.

Metastatic Breast Cancer Network is a national, independent, nonprofit, all volunteer patient advocacy group dedicated to the unique concerns of the women and men living with metastatic breast cancer. 

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.

(back to top)

Back to XRAYS Home

FORCE:Facing Our Risk of Cancer Empowered