Pennsylvania University. US: Targeted Therapy Drug Recently Approved by FDA for Use in Newly Metastatic Breast Cancer Patients.
Palbociclib, an investigational oral medication that works by blocking
molecules responsible for cancer cell growth, is well tolerated and
extends progression-free survival (PFS) in newly diagnosed, advanced
breast cancer patients, including those whose disease has stopped
responding to traditional endocrine treatments. Results of the phase II
study, led by researchers in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania, were published this month in Clinical Cancer Research.
Earlier phase I results by researchers at Penn Medicine contributed to
the development of palbociclib, which was recently approved by the
U.S. Food and Drug Administration (FDA) for metastatic breast cancer
patients just beginning to undergo endocrine therapy.
“The FDA approval has expanded treatments options for many
metastatic breast cancer patients, but these new results are showing
how effective the drug can also be for breast cancer patients who have
already tried endocrine therapies and may be running out of options,”
said lead investigator Angela DeMichele, MD, MSCE,
associate professor in the division of Hematology/Oncology and
Epidemiology and co-leader of the Breast Cancer Research Program at the
Abramson Cancer Center. “Combined with the promising results from
other trials looking at the effectiveness of this drug, our results
indicate that palbociclib can extend the duration of disease control
and produce tumor shrinkage in patients with estrogen-receptor positive
(ER+) breast cancer, without the debilitating side effects of
chemotherapy.”
The newly-published phase II trial primarily sought to evaluate
disease response and control, while monitoring for the presence of side
effects such as neutropenia, an abnormally low white blood cell count.
Patients enrolled in the trial had previously undergone several prior
chemotherapy and hormonal regimens for metastatic disease. Palboclib
was administered once daily for 21 days each month.
Overall, researchers noted a median PFS, the time before a tumor
worsens or the patient dies, of 3.7 months for patients taking the
drug. However, patients with hormone receptor-positive (HR+) breast
cancer – where the breast cancer cells depend on the hormones estrogen
and progesterone to grow – had significantly longer PFS (5.1 months)
compared to that of the HR-negative group (84 percent and 11 percent of
the enrolled population, respectively). And those who had previously
progressed through at least two rounds of hormonal therapy saw
significantly greater benefits, suggesting substantial activity in the
setting of acquired endocrine resistance.
Though some patients experienced low white blood cell counts or
other side effects, symptoms were managed with dose reductions, and
improvements in tumor shrinkage and disease control were still noted.
“The drug was extremely well-tolerated in this trial, and the
absence of symptoms commonly associated with cancer treatment, such as
nausea, diarrhea, or pain was remarkable,” said senior author Peter O’Dwyer, MD,
a professor in the division of Hematology/Oncology. “Further, since
dose reduction effectively restored normal neutrophil counts, safe
administration of effective doses was easily accomplished.”
Only a small number of patients enrolled in the trial had triple
negative breast cancer, all of whom rapidly progressed on treatment and
had to discontinue participation. However, ongoing studies by DeMichele
and her colleague, Amy Clark, MD,
a clinical instructor in the division of Hematology/Oncology, are
demonstrating potential benefits to palbociclib in ER-negative breast
cancer when it is given in combination with paclitaxel.
“This approach takes advantage of the ability of palbociclib to
synchronize cells within the cell cycle, potentially increasing the
percentage of cells sensitive to the cytotoxic effects of traditional
chemotherapy,” Clark explains. “Moreover, palbociclib may be effective
in other types of cancer that operate by a similar mechanism. These
trials are currently ongoing.”
Other Penn authors on the study include Kay See Tan, Daniel
Heitjan, PhD, Kristi Gramlich, Maryann Gallagher, Priti Lal, MD, Michael
Feldman, MD, Paul Zhang, MD, Christopher Colameco, David Lewis,
Melissa Langer, Noah Goodman, Susan Domchek, MD, Keerthi Gogineni, MD,
Mark Rosen, MD, and Kevin Fox, MD.
This study was funded through the Penn-Pfizer Alliance; Pfizer
provided funding for the study and palbociclib, but did not participate
in data collection, analysis, or writing of the manuscript. The authors
report no financial conflicts of interest.