Faslodex Plus Ibrance Better Than Faslodex Alone for Metastatic, Hormone-Receptor-Positive Disease: Final Analysis of PALOMA-3 Study

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The targeted therapy Ibrance (chemical name: palbociclib) was approved by the U.S. Food and Drug Administration in February 2015 to be used in combination with the hormonal therapy medicine Femara (chemical name: letrozole) to treat locally advanced-stage or metastatic, hormone-receptor-positive, HER2-negative breast cancer that hadn’t been treated with hormonal therapy before in postmenopausal women.

A study has found that Ibrance combined with the hormonal therapy Faslodex (chemical name: fulvestrant) more than doubled progression-free survival compared to Faslodex alone in women diagnosed with hormone-receptor-positive, HER2-negative metastatic breast cancer that had grown while being treated with hormonal therapy.

Called PALOMA-3, the final analysis of the study was published online on March 2, 2016 by the journal Lancet Oncology. Read the abstract of "Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial."

Doctors call the first medicine recommended to treat a disease a first-line treatment. If the first medicine doesn’t work, stops working, or causes unacceptable side effects, then doctors recommend a different treatment. This is called a second-line treatment.

When Ibrance was approved in February 2015, it was approved as a first-line treatment. The PALOMA-3 study strongly suggests that Ibrance offers benefits as a second-line treatment. The PALOMA-3 study doesn’t apply to women who are getting or who got Ibrance as a first-line treatment.

Progression-free survival is how long women live without the cancer growing.

Ibrance is a cyclin-dependent kinase 4/6 inhibitor. A kinase is a type of protein in the body that helps control cell division. Ibrance works by stopping cancer cells from dividing and growing.

Faslodex is an estrogen receptor downregulator. Faslodex sits in the estrogen receptor in breast cells so the cell can’t receive estrogen’s signals to grow and multiply. Faslodex also reduces the number of estrogen receptors and changes the shape of breast cell estrogen receptors so they don’t work as well.

The PALOMA-3 study included 521 women diagnosed with metastatic, hormone-receptor-positive, HER2-negative breast cancer that had come back or grown while being treated with hormonal therapy. Half the women were older than 57 and half the women were younger than 57. About 80% of the women were postmenopausal. About 23% had been diagnosed with metastatic disease when first diagnosed.

The women were randomly assigned in a 2:1 ratio to receive one of two treatments:

  • Ibrance (125 mg per day for 3 weeks, followed by 1 week off) and Faslodex (500 mg injection every 2 weeks for the first three injections and then one injection every 4 weeks)
  • Faslodex plus placebo (a sugar pill that looked just like Ibrance)

Women who were premenopausal also got Zoladex (chemical name: goserelin), a hormonal therapy medicine that stops the ovaries from making estrogen. Doctors sometimes call this medical ovarian shutdown. In other words, Zoladex made the premenopausal women postmenopausal for the length of the study. Zoladex is given by injection every 4 weeks.

In their final analysis, the researchers found a big difference in progression-free survival between the two treatment groups:

  • progression-free survival was 9.5 months for women treated with Ibrance and Faslodex
  • progression-free survival was 4.6 months for women treated with Faslodex alone

The study met its goal of better progression-free survival. Still, the researchers are continuing to follow the women to collect information on overall survival -- how long the women live, with or without the cancer growing. Right now, it’s not clear if better progression-free survival translates into better overall survival.

Ibrance didn’t cause any new or unexpected side effects in the PALOMA-3 study. The most common side effects seen in the study were:

  • neutropenia (low white blood cell counts)
  • fatigue
  • nausea

While the rates of neutropenia were higher in women treated with Ibrance -- 65% of those women compared to 1% of the women treated only with Faslodex -- the rates of fatigue and nausea were similar between the two treatment groups.

"This is a significant achievement because patients who fail to respond to endocrine therapy usually require chemotherapy for treatment with a compromise on quality of life," said first author Massimo Cristofanilli, M.D., professor of medicine at Northwestern University Feinberg School of Medicine. "The current study provides an effective and less toxic option for the most common type of metastatic breast cancer.

"The patients in this study who received the combination treatment experienced a better quality of life than those who received the standard endocrine therapy. The study also included patients who received chemotherapy," he continued. "This treatment also comes without chemotherapy's typical side effects, which may include complete hair loss and neuropathy."

"Our research underlines the effectiveness of palbociclib with fulvestrant in metastatic breast cancer and, importantly, demonstrates its benefit in all types of hormone-receptor-positive breast cancer," said Dr. Nicolas Turner, team leader in molecular oncology at The Institute of Cancer Research in London and co-lead author. "We hope our results lead to the adoption of this drug combination in breast cancer, where it delays the need to start chemotherapy by an average of 9 months."

If you’ve been diagnosed with metastatic, hormone-receptor-positive, HER2-negative breast cancer that has come back or grown while being treated with hormonal therapy, you may want to talk to your doctor about this study. Treatment with a regimen that includes Ibrance may be an option based on the results of this study. Ask your doctor if Ibrance might be a good option for you and your unique situation.

For more information, visit the Ibrance page in the Breastcancer.org Targeted Therapies section.

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