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 postmenopausal women diagnosed with hormone-receptor-positive, HER2-negative advanced-stage breast cancer that had grown while being treated with first-line hormonal therapy.
The study, called PALOMA3, was presented on June 1, 2015 at the American Society for Clinical Oncology (ASCO) Annual Meeting and published online on the same day by the New England Journal of Medicine:
- Read the ASCO Annual Meeting abstract of “PALOMA3: A double-blind, phase III trial of fulvestrant with or without palbociclib in pre- and post-menopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy”
- Read the New England Journal of Medicine article “Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer”
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 PALOMA3 study strongly suggests that Ibrance offers benefits as a second-line treatment. The PALOMA3 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 PALOMA3 study included 521 women diagnosed with advanced-stage, 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.
The researchers did an interim analysis of the results in December 2014 and found a big difference in progression-free survival between the two treatment groups:
- progression-free survival was 9.2 months for women treated with Ibrance and Faslodex
- progression-free survival was 3.8 months for women treated with Faslodex alone
Because the study met its goal of better progression-free survival, it was stopped early. 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 adding Ibrance to Faslodex will improve overall survival.
Ibrance didn’t cause any new or unexpected side effects in the PALOMA3 study. The most common side effects seen in the study were:
- neutropenia and leukopenia (low white blood cell counts)
While the rates of neutropenia and leukopenia were higher in women treated with Ibrance -- 78.8% of those women compared to 3.5% of the women treated only with Faslodex -- the rates of fatigue and nausea were similar between the two treatment groups.
"These are women with advanced metastatic cancer whose disease was kept in check without the use of toxic and life-disrupting chemotherapy," said Massimo Cristofanilli, M.D., director of the Breast Care Center at Thomas Jefferson University and senior author of the study. "This is a major advance for this population of women for which we had very few active options and are often treated with chemotherapy alone. Although palbociclib has yet to be approved for this population of women, this study is likely to be practice-changing. I don't envision a situation where single-agent endocrine therapy would be appropriate any longer for estrogen-receptor-positive, HER2-negative, metastatic breast cancer patients."
If you’ve been diagnosed with advanced-stage, 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.
And stay tuned to Breastcancer.org for the latest information on Ibrance and how it’s being used to treat breast cancer.
Editor’s Note: On April 4, 2019, the FDA expanded the use of Ibrance so the medicine now can be used to treat men diagnosed with advanced-stage or metastatic hormone-receptor-positive, HER2-negative breast cancer.