This article is more than 5 years old. Information may no longer be current.
Talazoparib improves PFS over chemotherapy for patients with BRCA mutations
Click Here to Manage Email Alerts
SAN ANTONIO — The PARP inhibitor talazoparib improved PFS over investigator’s choice chemotherapy among patients with advanced breast cancer and a BRCA germline mutation, according to results of the phase 3 EMBRACA study presented at the San Antonio Breast Cancer Symposium.
“Oral talazoparib [BMN 673, Pfizer] for patients with BRCA mutations has met its primary endpoint of improvement in PFS,” Jennifer K. Litton, MD, breast medical oncologist in the division of cancer medicine at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “We are very pleased that the phase III EMBRACA trial — the largest randomized clinical trial conducted in this group of patients with hereditary breast cancer — met its primary efficacy endpoint.”
Talazoparib — a highly potent, dual-mechanism PARP inhibitor — inhibits the PARP enzyme and effectively traps PARP on single-stranded DNA breaks, which prevents DNA damage repair and causes cell death in BRCA1/BRCA2-mutated cells.
In the multinational, phase 3, open-label study, researchers compared 1 mg oral talazoparib (n = 287; median age, 45 years) with physician’s choice of chemotherapy (n = 144; median age, 50 years), which included capecitabine, eribulin (Halaven, Eisai), gemcitabine, or vinorelbine.
Litton noted that capecitabine and eribulin were the most commonly used of these drugs.
“This was an open-label trial because there were both oral and IV chemotherapies in the physician’s choice arm,” Litton said during a press conference.
In addition to PFS, researchers also explored OS, overall response rate and safety, along with exploratory analyses of duration of response for responders and quality-of-life parameters.
Median follow-up was 11.2 months. Patients in the talazoparib arm were treated for a median of 6.1 months, whereas those in the chemotherapy were treated for 3.9 months.
Results showed a median PFS of 8.6 (95% CI, 7.2-9.3) months for the talazoparib group and 5.6 (95% CI, 4.2-6.7) months for the chemotherapy arm (HR = 0.54; 95% CI, 0.41-0.71).
“The curves do separate early and the separation continues,” Litton said. “The HR is statistically significant.”
Subgroup analysis results showed that the PFS response for talazoparib remained favorable among patients with BRCA mutations, triple-negative or hormone receptor-positive receptor status, and platinum treatment experience. Talazoparib particularly improved PFS among patients with a history of central nervous system metastasis (HR = 0.32; 95% CI, 0.15-0.68).
OS data are currently immature, with only 51% of projected events, Litton added. However, she noted a median OS of 23.3 months (95% CI, 18.1-26.2) in the talazoparib arm and 19.5 months (95% CI, 16.3-22.4) for the chemotherapy arm (HR = 0.76; 95% CI, 0.54-1.06).
“The HR does favor talazoparib,” Litton said in an interview. “It does not reach statistical significance, but the curves are really intriguing, because they do really separate at the end. It will be important to follow this as the data mature. There are still more patients on the talazoparib arm than physician’s choice arm.”
Regarding secondary and exploratory endpoints, Litton noted higher rates of confirmed complete response (5.5% vs. 0%) and partial response (57.1% vs. 27.2%) in the talazoparib arm compared with the chemotherapy arm. Objective response by investigator (OR = 4.99; 95% CI, 2.9-8.8) and clinical benefit rate (OR = 4.28; 95% CI, 2.7-6.83) also favored talazoparib, according to Litton.
Duration of response also favored talazoparib (median, 5.4 months vs. 3.1 months; HR = 0.43; 95% CI, 0.27-0.7).
The most common toxicity was anemia. Regarding nonhematological events, alopecia occurred at an equal rate between the two study arms.
Quality-of-life assessment — as evaluated by Patient-Reported Global Health Status — showed a statistically significant benefit with talazoparib, with a 3-point (95% CI, 1.2-4.8) improvement in that arm, vs. a –5.4 drop (95% CI, –8.8 to 2; P < .0001) with chemotherapy.
Time to deterioration also favored the study drug, according to Litton.
“Patients in the talazoparib arm actually experienced an increase in quality of life,” she told HemOnc Today. “Patients in the physicians’ choice arm showed deterioration.” – by Rob Volansky
Reference:
Litton JK, et al. Abstract GS6-07. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: Litton reports research funding from AstraZeneca, EMD Serono, Genentech and Pfizer, and advisory board roles with AstraZeneca and Pfizer, all uncompensated. Please see the abstract for all other authors’ relevant financial disclosures.