CHICAGO — The combination of palbociclib plus exemestane with ovarian suppression significantly prolonged PFS compared with capecitabine in premenopausal women with hormone receptor-positive breast cancer, according to study results presented at the ASCO Annual Meeting.
“Endocrine treatment is the preferred standard recommendation by clinical guidelines in premenopausal as well as postmenopausal women with HR-positive, HER2-negative metastatic breast cancer,” Yeon Hee Park, MD, from Samsung Medical Center in South Korea, said during her presentation.
“However, in the real world, 30% to 65% of patients with HR-positive, HER2-negative metastatic breast cancer are still treated with chemotherapy in earlier lines across the U.S., European countries and Korea,” she continued. “Capecitabine monotherapy is one of the most popular chemotherapy options in patients with HER2-negative metastatic breast cancer, with proven efficacy and safety profiles in prospective studies.”
However, the comparative efficacy of endocrine therapy and chemotherapy has not been evaluated, according to Park.
The researchers conducted a multicenter, open-label, phase 2 study to examine the safety and clinical antitumor activity of exemestane (Aromasin, Pfizer) plus a gonadotropin-releasing hormone (GnRH) agonist combined with palbociclib (Ibrance, Pfizer) compared with capecitabine among a cohort of 184 patients with premenopausal HR-positive metastatic breast cancer (mean age, 44 years).
Prior treatment for metastatic breast cancer with one line of chemotherapy was permitted. Patients with de novo metastatic disease “should have been treated with tamoxifen before enrollment,” according to the researchers.
Participants were randomly selected to receive either chemotherapy (n = 92) or endocrine therapy combined with palbociclib (n = 92). Patients in the chemotherapy arm received 1,250 mg/m² of capecitabine twice daily from day 1 to day 14 every 3 weeks. Patients in the combination arm received 25 mg exemestane for 28 days and 125 mg palbociclib for 21 days every 4 weeks plus a GnRH agonist.
PFS served as the primary endpoint. The follow-up period lasted a median of 14 months.
Patients treated with endocrine therapy plus palbociclib had a greater median PFS than those treated with capecitabine (19 vs. 11.3 months; P = .0493 by log-rank test; HR = 0.643).
In the advanced setting, 49% of patients receiving combination therapy and 51% of those receiving capecitabine were treatment naive.
It was significantly more common for patients in the palbociclib arm to experience grade III or higher hematologic toxicities than those in the capecitabine arm (60.9% vs. 19.2%; P < .0001). Patients treated with capecitabine were more likely to experience diarrhea (11% vs. 38%) and hand-foot disorders (1% vs. 76%) than those receiving combination therapy.
“This is the first study evaluating the CDK4/6 inhibitor palbociclib combined with endocrine therapy compared with single-agent capecitabine exclusively in premenopausal women,” Park concluded. “Palbociclib plus exemestane with ovarian suppression is an active treatment option in tamoxifen-pretreated premenopausal women with ER-positive, HER2-negative, metastatic breast cancer.” – by Alaina Tedesco
Park YH, et al. Abstract 1007. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Park reports receiving consulting or advisory fees from Pfizer; honoraria from Merck, Novartis and Pfizer; research funding from AstraZeneca, Eisai and Pfizer; and travel, accommodations and expenses from Merck and Novartis. Please see the abstract for all other authors’ relevant financial disclosures.