Experimental Palbociclib May Help Treat Estrogen-Receptor-Positive, HER2-Negative Advanced-Stage Breast Cancer

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An early study suggests that the experimental medicine PD 0332991, also called palbociclib, given in combination with Femara (chemical name: letrozole) offers more benefits in treating advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer than Femara alone.

The study, “Final results of a randomized Phase II study of PD 0332991, a cyclin-dependent kinase (CDK)-4/6 inhibitor, in combination with letrozole vs letrozole alone for first-line treatment of ER+/HER2- advanced breast cancer (PALOMA-1; TRIO-18),” was presented at the American Association for Cancer Research Annual Meeting on April 6, 2014.

Palbociclib is a cyclin-dependent 4/6 kinase inhibitor. A kinase is a type of protein in the body that helps control cell division. Palbociclib 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 palbociclib and Femara are pills taken by mouth.

In this small, early study, 165 postmenopausal women diagnosed with advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer were randomly assigned to be treated with either Femara plus a placebo (a sugar pill) or Femara plus palbociclib. The study was broken into two parts:

  • part one included 66 women
  • part two included 99 women who were specially selected for the study because the breast cancer they were diagnosed with had large amounts of a specific protein, cyclin-D1, or low amounts of another protein, p16; the cyclin-D1 protein helps cancers grow and the p16 protein helps stop cancer growth

Earlier studies done on cells in a lab suggested that palbociclib was most effective against estrogen-receptor-positive, HER2-negative breast cancer cells that had high levels of cyclin-D1 and low levels of p16.

The researchers wanted to know if Femara plus palbociclib would lengthen the time the women lived before the cancer grew. Doctors call this progression-free survival. The results suggest that the combination of Femara and palbociclib doubled progression-free survival time:

  • women who got Femara plus palbociclib lived about 20.2 months before the cancer grew
  • women who got Femara alone lived for about 10.2 months before the cancer grew

The women who were specially selected for the study because of cancer characteristics didn’t get any more benefits from the Femara-palbociclib combination than women who weren’t specially selected. The researchers aren’t sure why these women didn’t get more benefits.

The researchers also looked to see if adding palbociclib to Femara improved overall survival -- the time the women lived whether or not the cancer grew. Women who got palbociclib and Femara lived about 4 months longer than women who got Femara alone. Still, this difference wasn’t statistically significant, which means it could have happened by chance and not because of the difference in medicines.

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

  • low white blood cell count (neutropenia and leukopenia)
  • fatigue
  • anemia (low red blood cell count)

Overall, 13% of the women who got Femara and palbociclib dropped out of the study because of side effects compared to 2% of the women who got Femara alone.

This study was a phase II trial. Phase II trials look at how effective a new treatment is. If a certain percentage of people in a phase II trial get benefits from the new treatment and the side effects are acceptable, the new treatment will likely go on to a phase III trial.

Phase III trials of palbociclib have already started. Phase III trials compare the safety and effectiveness of a new treatment to the current standard of care. Phase III trials are usually large and done at many different locations. A phase III trial is the last step a new treatment goes through before the U.S. Food and Drug Administration considers approving for general use.

One phase III is looking at a combination of palbociclib and Femara and another is looking at combining palbociclib with Faslodex, another hormonal therapy medicine.

While the results of this study are promising, they are early results and many experts believe more research is necessary before doctors can use palbociclib to treat breast cancer.

Breastcancer.org Professional Advisory Board member Dr. Eric Winer, director of the breast oncology center at the Dana-Farber Cancer Institute’s Gillette Centers for Women’s Cancer and associate professor of medicine at Harvard Medical School, said larger studies were needed in an interview in The New York Times.

“This is a small phase II trial -- not tiny, but not the kind of study that would typically lead to a change in practice,” he said.

If you’re being treated for advanced-stage, estrogen-receptor-positive, HER2-negative breast cancer, you and your doctor may be considering a number of options, especially if the cancer has stopped responding to standard treatments. Treatment with an experimental regimen that includes palbociclib may be an option if you’re willing to participate in a clinical trial. Ask your doctor if there are any clinical trials that might be a good fit for you and your unique situation. Visit the Breastcancer.org Clinical Trials pages for more information.

And stay tuned to Breastcancer.org for the latest information on palbociclib and other new breast cancer treatments.

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

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