NEW ORLEANS — Short-term preoperative therapy with palbociclib appeared to decrease Ki67 cellular proliferation in women with early-stage breast cancer, according to results of a randomized trial presented at the American Association for Cancer Research Annual Meeting.
“The use of targeted therapies has been increasing in the last few years,” Monica Arnedos, MD, assistant professor of medicine at Gustave Rousey Cancer Campus in Villejuif, France, said in a press release. “It is crucial to determine that these drugs do hold activity against cancer cells. In the case of palbociclib [Ibrance, Pfizer], no predictive biomarkers have been identified to date.”
Palbociclib is approved in combination with letrozole to treat postmenopausal women with ER-positive, HER-2–negative metastatic breast cancer; however, no data exist on its efficacy in the early-stage setting.
The analysis included data from 100 women who underwent surgery for early-stage breast cancer. The majority of patients (93%) had hormone receptor-positive disease and 8% had HER-2–positive breast cancer.
The researchers randomly assigned patients 3:1 to 125 mg daily oral palbociclib for 14 days until the day before surgery (n = 74), or to no presurgical treatment (n = 26). They extracted formalin-fixed paraffin-embedded and frozen samples at baseline and at time of surgery.
Immunostaining of Ki67, RB, pRB, pAKT and pER; fluorescence in situ hybridization; and gene expression arrays were performed before and after treatment, with PIK3CA and p53 mutations assessed prior to treatment.
Antiproliferative response — defined as a natural logarithm of Ki67 below 1 at day 15 — served as the primary study objective.
Women assigned palbociclib exhibited significantly decreased pRB (P = .0027), and a greater proportion of women in the palbociclib arm experienced an antiproliferative response (58% vs. 10%; P = .0003).
Women in the palbociclib arm also had a significantly higher mean decrease in Ki67 on day 15 (P < .0001).
Researchers found the change in Ki67, a marker of cell proliferation, was greatest among women with hormone receptor-positive, HER-2–negative breast cancer. Among these women, 72% in the palbociclib arm demonstrated decreased Ki67 compared with 5% of the control arm.
The researchers did not observe a Ki67 response in women with triple-negative or HER-2–positive breast cancer (P = .0038 for interaction test).
Baseline RB, pRB or p16 status did not predict palbociclib’s effect on Ki67 status. However, palbociclib’s effect in Ki67 correlated with pRB changes from baseline (Spearman rank correlation, r = 0.42; P < .0001).
Arnedos acknowledged the small number of patients with HER-2–positive breast cancer as a study limitation.
Additional genetic analyses remain ongoing.
“Palbociclib works in untreated early-stage breast cancer,” Arnedos said. “[T]he magnitude of this activity was higher than expected.” – by Cameron Kelsall
Arnedos M, et al. Abstract CT041. Presented at: American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans.
Pfizer and the Breast Cancer Research Foundation funded this study. Arnedos reports research funding from Pfizer during the conduct of the study, as well as honoraria from Novartis.