The CDK4/6 inhibitor Ibrance (palbociclib), when added to hormone therapy normally given to certain advanced breast cancer patients, considerably benefits these people, researchers at the University of California, Los Angeles (UCLA), reported in an article that detailed their findings in a Phase 3 clinical trial combining this breakthrough drug with Femara (letrozole).
Specifically, trial results showed that Ibrance plus Femara significantly delayed cancer progression in postmenopausal women with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, without the severe side effects associated with Femara monotherapy.
The Phase 1 and Phase 2 trials that preceded this study were the basis for the U.S. Food and Drug Administration (FDA) approving Ibrance in combination with Femara for postmenopausal women with ER-positive, HER2-negative advanced breast cancer in February 2015, and for its European approval in that same indication earlier this month.
The Phase 3 clinical trial and its study, “Palbociclib and Letrozole in Advanced Breast Cancer,” published in The New England Journal of Medicine, seems to place Ibrance on a track for worldwide approval.
Ibrance, developed by Pfizer, is designed to prevent cells from dividing by targeting a family of proteins, CDK4/6, that are critical for cell proliferation.
The earlier, multi-year trials had shown that combining Ibrance with Femara led to a significant increase in progression-free survival compared to patients receiving Femara alone.
In addition, the Phase 2 study revealed that patients receiving Ibrance plus Femara survived without side effects almost two times longer than those receiving Femara alone (20.2 months vs. 10.2 months), accounting for a 42 percent reduction in the risk of disease progression.
Now, data from the Phase 3 trial (NCT01740427) has confirmed those results.
“The results from both studies are really remarkable for the degree of benefit they provide in slowing the growth of estrogen-receptor positive breast cancer,” Dr. Dennis Slamon of the UCLA Jonsson Comprehensive Cancer Center, director of the Revlon/UCLA Women’s Cancer Research Program, and director of clinical and translational research at the Jonsson Cancer Center, said in a press release. “The drug combination is very well tolerated and without the side effects of traditional chemotherapy, such as infections, nausea and significant hair loss.”
The study enrolled 666 women with ER-positive, HER2-negative breast cancer who had not received prior systemic therapy, who were randomized to receive Femara with or without Ibrance.
Results showed that the drug combination increased patients’ progression-free survival from 14.5 months to over 25 months, compared to the Femara monotherapy.
According to the researchers, such significant results had never been seen in randomized Phase 3 trials for women with ER-positive breast cancer.
“These results are a truly meaningful advancement for women in this patient population,” said Dr. Richard Finn, from the UCLA Jonsson Comprehensive Cancer Center, and an associate professor of medicine in the David Geffen School of Medicine at UCLA. “The results of the phase 3 study will support the full approval of palbociclib in the United States and around the world.”
Ibrance was also recently FDA-approved for use with Faslodex (fulvestrant), another hormone drug, in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose disease is advancing despite endocrine therapy.