Phase III Results Support Accelerated Approval for Ibrance

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On Feb. 3, 2015, the U.S. Food and Drug Administration (FDA) granted accelerated approval for using the targeted therapy Ibrance (chemical name: palbociclib) in combination with Femara (chemical name: letrozole) to treat locally advanced-stage or metastatic, estrogen-receptor-positive, HER2-negative breast cancer that hadn’t been treated with hormonal therapy before in postmenopausal women.

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.

Femara is an aromatase inhibitor, a type of hormonal therapy medicine. Femara works by stopping the production of estrogen in postmenopausal women. This means that less estrogen is available to stimulate the growth of hormone-receptor-positive breast cancer cells.

Both Ibrance and Femara are pills taken by mouth.

The FDA approval is based on results from the PALOMA-1 trial, which was a phase II trial that involved 165 women, which found that postmenopausal women diagnosed with advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer treated with the combination of Ibrance and Femara lived twice as long without the cancer growing compared to women who got only Femara. Doctors call the length of time a woman lives without the cancer growing “progression free survival.”

  • Women who got Ibrance plus Femara lived about 20.2 months before the cancer grew.
  • Women who got Femara alone lived about 10.2 months before the cancer grew.

Results from PALOMA-2, a phase III trial, confirm the PALOMA-1 results and “very clearly justifies the approval in the U.S. of this agent,” said Nancy Davidson, M.D., of the University of Pittsburgh Cancer Institute and current president of the American Association for Cancer Research.

The results were presented on June 8, 2016 at the 2016 American Association of Clinical Oncology annual meeting. Read the abstract of “PALOMA-2: Primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2- advanced breast cancer (ABC).

Phase II trials look at how effective a new treatment is. Phase II trials are slightly larger than phase I trials and usually involve 25 to 100 people. Researchers start with the dose and method of giving the new treatment that were found to be best in phase I. The phase II participants are given the new treatment and the researchers watch to see if the treatment has some benefit. If a certain percentage of participants benefit from the treatment and the side effects are still acceptable, the new treatment will probably go on to a phase III trial.

Phase III trials compare the safety and effectiveness of a new treatment to the current standard of care, in this case Femara alone. Phase III trials are usually large and are done at many sites. Usually, a phase III trial is the last step a new treatment goes through before the FDA considers approving it. Though if a treatment seems particularly promising, the FDA may grant accelerated approval, which is what the agency did for Ibrance.

In the PALOMA-2 trial, 666 postmenopausal women diagnosed with advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer that hadn’t been treated with hormonal therapy were randomly assigned to get one of two treatments:

  • Ibrance plus Femara
  • Femara plus a placebo (a sugar pill that looked just like Ibrance)

As in the PALOMA-1 trial, the researchers looked to see how long the women lived without the cancer growing. Doctors call this “progression-free survival.”

  • Progression-free survival was 24.8 months in women who got Ibrance plus Femara.
  • Progression-free survival was 14.5 months in women who got Femara plus placebo.

This difference was statistically significant, which means that it was likely because of the difference in treatment and not just due to chance.

The number of women who had a response to the combination of Ibrance and Femara also was higher compared to women who got Femara plus placebo:

  • 42% of women who got Ibrance plus Femara had a response to the treatment
  • 35% of women who got Femara plus placebo had a response to the treatment

Like most cancer medicines, Ibrance can cause side effects, some of them serious. In the PALOMA-2 trial, compared to women treated with Femara plus placebo, women treated with Ibrance plus Femara had more:

  • neutropenia and leukopenia (low white blood cell counts)
  • fatigue
  • nausea
  • hair loss

Overall, women treated with Ibrance plus Femara had more serious side effects than women treated with Femara plus placebo (19.6% vs. 12.6%). Nearly 10% of women treated with Ibrance plus Femara stopped treatment because of side effects compared to nearly 6% of women treated with Femara plus placebo.

If you’re a postmenopausal woman who’s been diagnosed with advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer that hasn’t been treated with hormonal therapy yet, you may want to ask your doctor about this study and if the combination of Ibrance and Femara makes sense for you and your unique situation. For more information, visit the Breastcancer.org Ibrance page.



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