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Study: Breast cancer outcomes improved with CDK4/6 inhibitor treatment

Summary

A study showed that people with metastatic breast cancer who took an oral drug known as a CDK4/6 inhibitor combined with hormone therapy did better than people who took hormone therapy alone. The drug combination improved the length of time before cancer worsened or returned. After six years of treatment, people who took this drug combination lived longer compared to those who took hormone therapy alone. (Posted 4/5/23)

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Breast cancer outcomes improved with CDK4/6 inhibitor treatment
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RELEVANCE

Most relevant for: People with HR-positive HER2-negative advanced breast cancer.
It may also be relevant for:

  • people with ER/PR + cancer
  • men with breast cancer

Relevance: High

Strength of Science: Medium-High

Research Timeline: Post Approval

Relevance Rating Details

What was the research about?

A large research study known as PALOMA-3 looked at how well a drug called Ibrance (palbociclib) works when combined with hormone therapy (fulvestrant) for people with breast cancer that was hormone sensitive (). In 2019, researchers shared early results from the study, which seemed to show that some people who received the two drugs together did better than people who received hormone treatment alone. However, these results were too early for researchers to say for certain that the drug combination worked better than hormone therapy alone.  

This follow-up report from 2022 looked at overall survival (how long participants lived) for a longer period of time. The report also looked at whether some groups of people benefitted more from the drug combination.

Study findings

Researchers looked at results for all participants and for different subgroups of participants.

All participants

In this updated report, overall survival continued to be better for people who were treated with Ibrance plus fulvestrant compared to people treated with fulvestrant alone:

  • 35 months for people on Ibrance plus fulvestrant
  • 28 months for people on fulvestrant alone

While the combination of fulvestrant plus Ibrance improved overall survival, the difference—a benefit of seven months at six years—was not statistically significant. (The overall survival reported in 2019 was the same for both groups.)

The benefit for participants who did not previously have chemotherapy
Among people who had not received prior chemotherapy, overall survival at 6 years was 40 months for people on Ibrance plus fulvestrant compared to 30 months for people on fulvestrant alone, a benefit of 10 months. This result was statistically significant.

Overall survival
  fulvestrant alone Ibrance plus fulvestrant
Full group 28 months 35 months
No chemotherapy 30 month 40 months

 

 

 

What does this mean for me?

If you have , metastatic breast cancer, treatment with a CDK4/6 inhibitor such as Ibrance combined with fulvestrant may be a treatment option. The combination of Ibrance plus fulvestrant increases the time before breast cancer returns or becomes worse compared to fulvestrant alone. While the research suggests that this drug combination may also increase how long patients live, the results are not statistically significant.   

Note: The issued a safety alert in September 2019, that the CDK4/6 inhibitors Ibrance (palbociclib), Kisqali (ribociclib) and Verzenio (abemaciclib) may cause a rare but severe inflammation of the lungs. 

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • What treatment therapy or therapies are best for me?
  • Should I consider treatment with a CDK4/6 inhibitor for my breast cancer?
  • What side effects might I have with a CDK4/6 inhibitor?
  • Should I have testing of my tumor?
  • Are there clinical trials enrolling participants with breast cancer that are appropriate for me?

Open clinical trials
Open clinical trials

The following studies look at treatment for people with ER-positive breast cancer.  

Other clinical trials for people with breast cancer can be found here.

Updated: 12/22/2023

Related resources
Related resources

The following organizations have resources related to breast cancer. 

Updated: 06/28/2023

Strengths and limitations

Strengths

  • This update followed participants for another 2 years. The collection of long-term data can confirm how well this drug combination treatment worked for participants who received it. Sometimes, long-term follow-up can also reveal additional side effects or interactions with other treatments.
  • This is the first study to look at whether circulating tumor mutations can help identify those who would benefit the most from a CDK4/6 inhibitor (Ibrance).

Limitations

  • In studies where participants tend to live longer, it is often hard to show that treatment significantly improved their overall survival. In this study, the researchers still do not know if the trend of increased overall survival among participants who received Ibrance plus fulvestrant was due to the treatment, some other factor or chance.
  • Because the researchers looked at small numbers of participants in subgroups (chemotherapy and circulating tumor ), they did not have enough data to conclude that improvement in overall survival was due to treatment rather than chance.

Context

Several studies have shown that the CDk4/6 inhibitors palbociclib (Ibrance), ribociclib (Kisquali) and abemaciclib (Verzenio) increase survival for people with , advanced breast cancer. Somewhat longer overall survival has been seen with abemaciclib in the MONACH2 trial and with ribociclib in the MONALEESA-3 trial (participants did not have prior chemotherapy in either trial).

  • MONARCH-2 trial: at 4 years, overall survival was:
    • 47 months with abemaciclib plus fluvestrant
    • 37 months with fluvestrant alone
  • MONALEESA-3 trial: at 4.5 years, overall survival was:
    • 54 months with ribociclib plus fulvestrant
    • 42 months with fulvestrant alone  

However, no head-to-head comparison of these three CDK4/6 inhibitors has been done as yet. All three CDK4/6 inhibitors are FDA-approved for postmenopausal people. Currently, Ibrance is the only CDK4/6 inhibitor approved for perimenopausal or premenopausal women. 

Note: The issued a safety alert on September 13, 2019, that Ibrance (palbociclib), Kisqali (ribociclib) and Verzenio (abemaciclib) may cause a rare but severe inflammation of the lungs.

Expert Guidelines
Expert Guidelines

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 as preferred treatments for ER-positive and breast cancer:

  • for people with or mutations:
    • The NCCN lists Lynparza () or () for people with an inherited or mutation. 
  • First line therapy
    • The NCCN lists as the preferred treatment combination of hormonal therapy (aromatase inhibitor or Fulvestrant) + with a CDK4/6 inhibitor:
      •  abemaciclib (Verzenio), palbocicib (Ibrance) or ribociclib (Kisqali). 
  • For second, third or later lines of therapy, the NCCN lists the following targeted therapies or combinations treatments:
    • 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 whose tumors are HER2-low ( 1+ or 2+), who received chemotherapy in the setting and their 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 or mutation
    • a combination of everolimus and hormonal therapy
    • hormonal therapy alone
    • Trodelvy (sacituzumab govitecan-hziy) for , cancers after prior treatment including hormone therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy (including a taxane)

Updated: 03/21/2023

Open Clinical Trials
Open Clinical Trials

The following studies are looking at treatment for people with advanced . 

 

Updated: 02/01/2024

Peer Support
Peer Support

The following organizations offer peer support services for people with, or at high risk for breast cancer:

Updated: 11/29/2022

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Article Rating Details

Study Rating Details

Relevance: High

  • The results of this clinical trial are relevant for people with metastatic breast cancer. 
  • Palbociclib is currently approved for FDA use with fulvestrant based on improvement in progression-free survival (earlier results). While overall survival was not statistically different between those who received the combination compared to those who received fluvestrant alone, it was clinically meaningful and trended toward increased overall survival.

Scientific Strength: Medium-High

  • This is a well-controlled prospective, randomized, double-blinded placebo-controlled study with long-term follow-up.
  • The analysis is sound and the conclusions are justified. The study authors provide context for their results and interpretation specifically regarding overall survival. The authors emphasize the clinical importance of the increase in overall survival. However, the lack of statistical significance means that this increase may either be due to chance and is not repeatable or it may be a true small difference. This study cannot determine which is the case.

Research Timeline: Post approval

  • The use of a CDK4/6 inhibitor is standard of care for people with HR-positive, HER2-negative advanced breast cancer. Ibrance is one of 3 approved CDK4/6 inhibitors.