Phase III Trial Confirms Palbociclib (Ibrance) Effective as First Treatment for Metastatic Breast Cancer

PALOMA-2 results show when paired with aromatase inhibitor and given as first treatment for metastatic disease, the CDK 4/6 inhibitor delays progression by a median 10 months in postmenopausal women with HR-positive, HER2-negative metastatic breast cancer
Breast Cancer News
November 28, 2016
Erin Rowley, Writer and Content Coordinator
Reviewed By: 
Sara Hurvitz, MD

Results of a phase III trialinfo-icon called PALOMA-2 show postmenopausalinfo-icon women with hormone receptorinfo-icon-positive, HER2-negative metastaticinfo-icon breast cancer don’t experience disease progressioninfo-icon as quickly when palbociclib (Ibrance) is added to treatment with the aromatase inhibitorinfo-icon letrozoleinfo-icon (Femarainfo-icon). The results appeared in the New England Journal of Medicine  on November 17.

Background and Goals

In February 2015, the FDAinfo-icon approved the targeted therapyinfo-icon palbociclib, in combination with the aromatase inhibitor letrozole, for postmenopausal women with estrogen receptor-positiveinfo-icon, HER2-negative metastatic breast cancer who hadn't been treated with hormonal therapyinfo-icon for metastatic breast cancer before. Palbociclib was the first cyclin-dependent kinase (CDK) 4/6 inhibitor to be approved by the FDA. CDK 4/6 inhibitors target two specific kinases, or enzymes, that help tumorinfo-icon cells grow and divide.

FDA approval usually comes after a phase III trial, but palbociclib was granted accelerated approval because of exciting results from a phase II trialinfo-icon, PALOMA-1. PALOMA-1 suggested that when paired with letrozole, palbociclib could double progression-free survivalinfo-icon (PFS), the time between starting treatment and the disease growing or spreading.

Phase III trials were done to confirm how well palbociclib works. Phase III trials involve more people than phase II trials, and they compare the treatment in question to the standard treatment, to see which works best. One of those phase III trials was PALOMA-3. It found that when paired with another anti-hormonal agent, fulvestrantinfo-icon (faslodexinfo-icon), palbociclib lengthened PFS in women with estrogen receptor-positive, HER2-negative metastatic breast cancer after the disease grew or spread while on other hormonal therapy treatment in the metastatic setting. The FDA approved palbociclib plus fulvestrant in February 2016.

Another phase III trial, PALOMA-2, was created to confirm the results of PALOMA-1. Those results are now available.


PALOMA-2 recruited postmenopausal women with hormone receptor-positive, HER2-negative breast cancer who had not yet started treatment for metastatic disease. A total of 666 women were assigned to treatment with

  • Daily palbociclib by mouth for cycles of 3 weeks on, 1 week off; and daily letrozole by mouth, OR
  • A daily placeboinfo-icon by mouth for cycles of 3 weeks on, 1 week off; and daily letrozole by mouth


The medianinfo-icon number of months of progression-free survival was

  • 24.8 in the group that received palbociclib and letrozole
  • 14.45 months in the group that received a placebo and letrozole

Severe side effects were seen in 19.6 percent of the palbociclib group versus 12.6 percent of the placebo plus letrozole group. By far, the most common moderate to severe side effectinfo-icon was low white blood cellinfo-icon counts, which raises the risk of infectioninfo-icon. These low counts, called neutropeniainfo-icon, were experienced by most people in the palbociclib group, but few people in the placebo plus letrozole group. But in spite of the high rates of neutropenia, infection was relatively uncommon.

About 10 percent of women in the palbociclib group stopped treatment because of side effects, versus about 6 percent in the group that didn’t take palbociclib.

What This Means For You

If you have already gone through menopauseinfo-icon and have hormone receptor-positive, HER2-negative metastatic breast cancer, it may comfort you to know that researchers have found new ways to treat people like you. You may also appreciate that they’ve now done a number of studies to prove how well those treatments work.

Talk to your oncologistinfo-icon about whether palbociclib is a good option for you. If you haven’t yet been treated for metastatic breast cancer, you may be able to get palbociclib plus letrozole. If you have already received hormonal therapy for metastatic breast cancer, you may be able to get palbociclib plus fulvestrant. Your oncologist can also talk to you about side effects.

Finn, R., Martin, M, Rugo, H., et al. Palbociclib and Letrozole in Advanced Breast Cancer. New England Journal of Medicineinfo-icon. November 17, 2016. doi: 10.1056/NEJMoa1607303.


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Additional Related Topics 
Hormone Receptor-Positive
Clinical Trials
Hormonal Therapy
Targeted Therapy