WASHINGTON, D.C.—Concern over a low white blood cell count discovered in African-American patients has led to the first clinical trial to test newly approved breast cancer drug palbociclib (Ibrance) specifically on African Americans only. The Georgetown Lombardi Comprehensive Cancer Center is currently enrolling candidates for the Phase 2 clinical trial, followed by five other institutions in Washington, D.C., Maryland, Alabama and New Jersey.
The upcoming trial has come about because roughly three-fourths of the 1,137 patients tested in earlier clinical trials of palbociclib developed neutropenia (low white blood cell count), including half of the patients who developed a more serious form of the disorder. The U.S. Food and Drug Administration (FDA) guidelines for palbociclib use require the patient to have a normal white blood cell count.
That threshold forces the elimination of African-American women who have “benign ethnic neutropenia,” or a lower-than-normal white blood cell count, from receiving the drug, according to Dr. Filipa Lynce, a physician researcher at Georgetown Lombardi.
The Phase 2 study Lynce is conducting explores the safety of the drug in all African-American women, knowing that some may already have benign ethnic neutropenia.
“The assumption that African-American women with this common condition could not safely use this drug needs to be fully tested,” says Lynce. “Since the Phase 2 study just opened, we expect to complete enrollment for this trial in 12 to 18 months.”
The Phase 2 study aims to evaluate the safety of palbociclib (Ibrance) in African-American patients, including those who may have a low white blood cell count due to benign ethnic neutropenia, Lynce says. This condition is common in African Americans, but it is unclear whether it increases a patient’s risk of infection while taking palbociclib.
“Palbociclib (Ibrance) is being prescribed to women of all races,” Lynce told DDNews. “The important point is that the majority of patients enrolled in the clinical trials that led to the FDA approval of palbociclib were Caucasians; therefore, it’s on Caucasian women that we have most of the efficacy and safety data.”
However, Lynce could not say how many of the 1,137 patients tested in earlier clinical trials of palbociclib were African Americans.
“We don’t have information available on who developed neutropenia by race,” Lynce says. “The vast majority of the patients in the trial were Caucasians.”
Palbociclib “has been shown to be very effective and is expected to approximately double the progression-free survival compared to hormonal therapy only,” she adds.
The Phase 2 study will enroll 35 patients with metastatic breast cancer at Georgetown Lombardi/MedStar Georgetown University Hospital; MedStar Washington Hospital Center; MedStar Union Memorial Hospital and MedStar Good Samaritan Hospital; the University of Alabama at Birmingham Comprehensive Cancer Center; and the John Theurer Cancer Center at Hackensack University Medical Center.
In the upcoming study, all patients will be given palbociclib and letrozole (Femara). Both agents are pills taken once daily. Participants will be enrolled in the study for a maximum of 13 months.
Lynce received a $600,000 grant from Pfizer, the developer of palbociclib, to test the agent in African Americans.
“I think this award (grant) shows how committed the company is to look at the safety of their drugs in minorities,” says Lynce. “One focus area of my research is to look at the safety and efficacy of medications used to treat breast cancer in populations that have not been included in past clinical trials.”
Palbociclib was initially approved in February 2015 for the treatment of estrogen receptor-positive, HER2-negative metastatic breast cancer in women who had not yet received endocrine therapy. The approval was granted under the FDA’s breakthrough therapy designation.
The additional indication for palbociclib is based on results from the PALOMA-3 trial, which was stopped early in April 2015 after an interim analysis showed benefit in combination with fulvestrant when compared to fulvestrant and placebo.
According to the findings, women who received palbociclib plus fulvestrant had a median progression-free survival of 9.5 months, compared with 4.6 months in the fulvestrant plus placebo group. The overall response rate was 24.6 percent with palbociclib, compared to 10.9 percent in the placebo group.
The duration of response was also longer with the study drug, at 9.3 months compared with 7.6 months in the fulvestrant plus placebo patients, the study says. The most common adverse events of any grade were neutropenia at 83 percent vs. only 4 percent in the placebo group, leucopenia (53 percent vs. 5 percent), infections (47 percent vs. 31 percent) and fatigue (41 percent vs. 29 percent).
“There currently is no cure for metastatic breast cancer, so ongoing treatment is usually needed to control the spread of the disease,” says Dr. Marisa Weiss, founder and chief medical officer of Breastcancer.org. “That’s why the availability of a first-of-its-kind treatment option like [palbociclib] for women dealing with HR-positive, HER2-negative metastatic disease represents a very important advance.”
