Combining the new breast cancer drug palbociclib with paclitaxel (Taxol) shrank tumors in nearly half of patient with estrogen-receptor (ER) positive breast cancer, according to new research from the Perelman School of Medicine at the University of Pennsylvania. The results will be presentedSaturday at the 2015 San Antonio Breast Cancer Symposium (Abstract P6-13-08). A second study(Abstract P4-13-04), to be presented Friday provides new clues to how breast cancer develops resistance to the palbociclib, a common occurrence among many patients who take the drug.

“Results of the first study found that palbociclib and paclitaxel can be safely combined on an alternating dosing schedule,” said Angela DeMichele, MD, MSCE, the Alan and Jill Miller Associate Professor in Breast Cancer Excellence in Penn's Abramson Cancer Center, and senior author on the study. “The high response rate we saw suggests this combination may hold benefits for patients over paclitaxel alone. Based on these results, a larger clinical trial to determine the benefits is warranted.”

A complementary therapy

Palbociclib targets the rapid division of tumor cells by inhibiting the activity of the enzymes CDK4 and CDK6, which help drive cell division and are upregulated in most cancers. The researchers suspected that palbociclib’s unique mechanism of action may make it a good partner for other breast cancer drugs such as paclitaxel, which kills dividing cells at a certain point in the cell division process (also known as the "cell cycle”). Palbociclib effectively halts the cell cycle before that point, and thus in principle can synchronize cancer cells in a way that makes them more vulnerable to a closely following dose of paclitaxel.

To begin to test this concept in the clinic, DeMichele and colleagues, including lead author Amy S. Clark, MD, MSCE, an assistant professor of Hematology-Oncology in the Abramson Cancer Center, treated 27 breast cancer patients with alternating doses of palbociclib – administered daily for several days at a time – and paclitaxel administered once per week. The researchers ultimately settled on an optimal palbociclib dose of 75 mg per day, combined with a standard dose of paclitaxel.

The chief aim of the study was to determine if this alternating dosing of the two drugs is safe enough to use in larger-scale trials. The results suggest this appeared to be the case. Though most participants developed the low-white-blood-cell count condition known as neutropenia, a common side-effect of palbociclib and other chemo drugs, DeMichele says in general it was not dangerous. Some participants had their palbociclib doses lowered as a result of the condition.