Adding Pfizer’s Ibrance (palbociclib) to standard treatment Faslodex (fulvestrant) significantly extended the survival of advanced breast cancer patients in a Phase 3 clinical trial, researchers report.

Called PALOMA-3, the trial  (NCT01942135) specifically tested if patients with hormone-receptor-positive (HR)-positive, human epidermal growth factor 2 (HER2)-negative metastatic breast cancer responded better to the combination than to AstraZeneca‘s Faslodex alone.

Trial findings were published in the study, “Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer,” in The New England Journal of Medicine.”

“The results of the study show that it is possible to improve and prolong the life of patients with hormone receptor-positive metastatic breast cancer. We now have solid data to suggest that this treatment should be the new standard of care,” lead author Massimo Cristofanilli, MD, said in a press release. Cristofanilli is a professor of hematology/oncology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician.

Most breast cancers are HR-positive, which means they depend on hormones, such as estrogen, to continue growing. These cancers are generally treated with hormone therapies like Faslodex that prevent estrogen from interacting with its receptor, reducing the growing signals to the tumors. However, after some time, patients can develop resistance to these medications.

Ibrance is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Cyclin-dependent kinases are molecules involved in cell division, making them crucial for tumor growth. Therapies that inhibit these molecules tend to work well in combination with hormone therapies.

The PALOMA-1 (NCT00721409) and PALOMA-2 (NCT01740427) clinical trials had already shown that Ibrance in combination with Femara (letrozole), another hormone therapy, increased the length of time patients survived without disease progression when used as a first-line treatment.

PALOMA-3 is a Phase 3 trial that evaluated the efficacy of the Ibrance-Faslodex combo in HR-positive, HER2–negative metastatic breast cancer patients whose disease progressed after receiving hormone therapy.

The trial evaluated 521 patients. About two-thirds (347) received Ibrance in combination with Faslodex, and one-third (174) received Faslodex in combination with placebo. The follow-up time was 44.8 months.

The primary objective was the duration of progression-free survival. A previous analysis of PALOMA-3 showed that the combination increased progression-free survival by almost five months compared with Faslodex alone. Based on these findings, the U.S. Food and Drug Administration approved the combination to treat advanced breast cancer in 2016.

This current study reports the results of PALOMA-3’s secondary goals, which included overall survival and time elapsed before the patients needed to undergo another treatment or go through chemotherapy.

On average, patients taking Ibrance and Faslodex survived 34.9 months versus 28 months for patients taking Faslodex and placebo. While this difference did not reach statistical significance, the improvement was deemed clinically meaningful.

“To design a trial in this context that would detect a significant improvement in overall survival … would have required a much larger trial,” the researchers said.

The benefits were more noticeable in patients who had previously responded to hormone therapy, with overall survival of 39.7 months for the Ibrance group and 29.7 months for the placebo group.

The time before another therapy was needed was similar between the two groups. However, the time until chemotherapy was needed in the Ibrance group was significantly longer than in the placebo group — 17.6 months versus 8.8 months.

“Typically, treatments for estrogen-positive metastatic breast cancer delay the progression of cancer but almost never prolong the life of patients. This treatment is the first of its kind to show such an important benefit,” Cristofanilli said.

Safety results were consistent to the primary analysis of PALOMA-3, with the most common adverse events in both groups being infections, fatigue, and excess aspartate aminotransferase — a liver enzyme. Severe or life-threatening low neutrophil levels were seen in 70% of those receiving the combination, but none of the patients in the Faslodex group.

“Taken together, the data from the PALOMA-3 trial showed that palbociclib in combination with fulvestrant led to a 6.9-month prolongation of overall survival, although the finding did not reach significance in the intention-to-treat population,” the researchers concluded in the study.

These results further support the idea that the combination of a CDK4/6 inhibitor with hormone therapy could be the standard treatment in patients who no longer respond to hormone therapy alone.