A study found that the targeted therapy Ibrance (chemical name: palbociclib) combined with the hormonal therapy Faslodex (chemical name: fulvestrant) improved overall survival by about 7 months compared to Faslodex alone in women diagnosed with hormone-receptor-positive, HER2-negative advanced-stage breast cancer that had grown while being treated with hormonal therapy.
The research was presented on Oct. 20, 2018, at the 2018 European Society for Medical Oncology (ESMO) Congress and published simultaneously in the New England Journal of Medicine.
- Read the ESMO abstract of “Overall survival (OS) with palbociclib plus fulvestrant in women with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-−) advanced breast cancer (ABC): Analyses from PALOMA-3.”
- Read the New England Journal of Medicine abstract of “Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer.”
Overall survival is how long the women lived, whether or not the cancer grew.
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. Ibrance is a pill taken by mouth.
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. Faslodex is a liquid that is given once a month as an injection into a muscle.
Advanced-stage breast cancer is breast cancer that has spread to tissue near the breast or to parts of the body away from the breast, such as the bones or liver.
PALOMA-3: Studying the best treatments for advanced-stage, hormone-receptor-positive, HER2-negative breast cancer
The study, called the PALOMA-3 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.
The women were randomly assigned in a 2:1 ratio to receive one of two treatments:
- 347 women were treated with 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)
- 174 women were treated with 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.
PALOMA-3 results published in 2016 found that adding Ibrance to Faslodex more than doubled progression-free survival compared to Faslodex alone. On the basis of these results, Ibrance and other cyclin-dependent kinase 4/6 inhibitors in combination with hormonal therapy have become the standard of care for advanced-stage, hormone-receptor-positive, HER2-negative breast cancer.
Progression-free survival is how long the women lived without the cancer growing.
Still, doctors wanted to know if the combination treatment improved overall survival.
For this overall survival analysis, the follow-up time was about 4 years.
Median overall survival was:
- 34.9 months for women treated with Ibrance and Faslodex
- 28.0 months for women treated with Faslodex alone
Median overall survival means that half the women lived for a longer time and half the women lived for a shorter time.
The researchers also looked at groups of women with specific characteristics to see if the combination of Ibrance and Faslodex offered more benefits for certain women.
For the 410 women who had responded to earlier hormonal therapy treatment, median overall survival was:
- 39.7 months for women treated with Ibrance and Faslodex
- 29.7 months for women treated with Faslodex alone
For the 111 women who were resistant to earlier hormonal therapy treatment, median overall survival was:
- 20.2 months for women treated with Ibrance and Faslodex
- 26.2 months for women treated with Faslodex alone
These results show that the combination of Ibrance and Faslodex worked best in women who previously responded to hormonal therapy.
"Here, we present the first-ever overall survival results from a phase III study for a CDK4/6 inhibitor in a pre-planned analysis of the PALOMA-3 trial,” said lead author Massimo Cristofanilli, professor of medicine at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Importantly, this is the first report demonstrating that the absolute gain in survival is similar to the absolute gain in progression-free survival in the whole population. Moreover, this prolongation of life is of a large magnitude in patients with prior sensitivity to endocrine therapy."
"It's incredibly rewarding that the benefits we had previously seen for palbociclib are now translating into such significant extensions in survival,” said Nicholas Turner, professor of molecular oncology at the Institute of Cancer Research in London, another study author. “This drug can offer women more precious time with their loved ones and because it is a targeted treatment, it is much kinder than chemotherapy and enables many women to carry on with their lives normally.”
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 and ask if treatment with a regimen that includes a cyclin-dependent kinase 4/6 inhibitor such as Ibrance, Kisqali (chemical name: ribociclib), or Verzenio (chemical name: abemaciclib) may be an option for you and your unique situation.
For more information on cyclin-dependent kinase 4/6 inhibitors, visit the Breastcancer.org Targeted Therapy section.
To discuss treatment options with others being treated for advanced disease, join the Breastcancer.org Discussion Board forum Stage IV and Metastatic Breast Cancer ONLY.
Editor's Note: This article was updated on Jan. 17, 2019, with additional information.
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.