Pfizer Inc. (NYSE:PFE) today announced that the Phase 3 EMBRACA trial in patients with germline (inherited) BRCA1/2-positive (gBRCA+) locally advanced and/or metastatic breast cancer (MBC) demonstrated superior progression-free survival (PFS) in patients treated with talazoparib, compared to patients who received physician’s choice standard of care chemotherapy. Median PFS was 8.6 months (95% CI: 7.2, 9.3) for patients treated with talazoparib and 5.6 months (95% CI: 4.2, 6.7) for those treated with chemotherapy [HR: 0.54 (95% CI: 0.41, 0.71), p<0.0001]. This represents a 46% reduction in the risk of disease progression. In addition, the proportion of patients achieving a complete or partial response (objective response rate) in the talazoparib group was more than twice that of the control arm (62.6% for talazoparib vs. 27.2% for chemotherapy [OR: 4.99 (95% CI: 2.9-8.8), p<0.0001]). Talazoparib is an investigational, oral, dual-mechanism poly ADP ribose polymerase (PARP) inhibitor that is taken once daily. The data will be presented today as an oral presentation at the 2017 San Antonio Breast Cancer Symposium.

"Patients with germline BRCA-positive breast cancer are typically diagnosed at a younger age than those with nonhereditary breast cancer, and there are no therapies specifically approved for them outside of current standard of care therapies," said Jennifer Litton, MD, lead investigator and associate professor in the breast medical oncology department of The University of Texas MD Anderson Cancer Center. "EMBRACA supports the potential of talazoparib to give these patients additional time without disease progression, compared to chemotherapy."

Pfizer will be discussing these data from EMBRACA, the largest Phase 3 trial performed to date of a PARP inhibitor in patients with gBRCA+ MBC, with worldwide health authorities. There are currently limited treatment options for patients with this molecular subtype.

"Results from the EMBRACA study are very encouraging and a great example of precision drug development. By enrolling only patients with germline BRCA-positive metastatic breast cancer, treatment with talazoparib reduced the risk of disease worsening by nearly half, compared with current standard of care chemotherapy. This includes heavily pretreated patients, those with hormone receptor-positive disease and those who had a history of brain metastases," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development.

The results of the EMBRACA trial also showed that the PFS benefit with talazoparib was consistent across prespecified subgroups, including hormone receptor (HR) status (triple negative [TNBC] or hormone receptor-positive [HR+]), BRCA mutation (1 or 2), prior chemotherapy (whether patients had none or up to three chemotherapies before talazoparib), and history of central nervous system (CNS) metastases. There also was a statistically significant delay in the time to clinically meaningful deterioration in global health status/quality of life with talazoparib versus chemotherapy (HR 0.38 [95% CI 0.26-0.55], p<0.0001), as measured by the EORTC QLQ-C30, a cancer-specific, patient-reported quality of life questionnaire.

Adverse events (AEs) observed with talazoparib were consistent with findings from previous trials. The most common AEs observed with talazoparib (any grade in at least 15% of patients) were anemia (52.8%), fatigue (50.3%), nausea (48.6%), neutropenia (34.6%), headache (32.5%), thrombocytopenia (26.9%), alopecia (25.2%), vomiting (24.8%), diarrhea (22%), constipation (22%), decreased appetite (21.3%), back pain (21%) and dyspnea (17.5%). The incidence of serious AEs was 31.8% in the talazoparib arm and 29.4% in the chemotherapy arm. Discontinuations due to AEs occurred in 7.7% of patients in the talazoparib arm and 9.5% of patients in the chemotherapy arm.

In addition to EMBRACA, talazoparib demonstrated promising activity in patients with gBRCA+ MBC in the Phase 2 ABRAZO trial. Patients in ABRAZO had either been previously treated with platinum-based chemotherapy or were heavily pretreated with at least three prior lines of non-platinum-based chemotherapy.1