14 CLINICAL STUDIES
EMBRACA Study (NCT01945775)
Deleterious or Suspected Deleterious Germline BRCA-mutated (gBRCAm) HER2-negative Locally Advanced or Metastatic Breast Cancer
EMBRACA (NCT01945775) was an open-label study in which patients (N=431) with gBRCAm HER2-negative locally advanced or metastatic breast cancer were randomized 2:1 to receive TALZENNA 1 mg or healthcare provider's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine) until disease progression or unacceptable toxicity. Randomization was stratified by prior use of chemotherapy for metastatic disease (0 versus 1, 2, or 3), by triple-negative disease status (triple-negative breast cancer [TNBC] versus non-TNBC), and history of central nervous system (CNS) metastasis (yes versus no).
Patients received no more than 3 prior cytotoxic chemotherapy regimens for their metastatic or locally advanced disease. Patients were required to have received treatment with an anthracycline and/or a taxane (unless contraindicated) in the neoadjuvant, adjuvant, and/or metastatic treatment setting. First-line treatment for advanced or metastatic disease with no prior adjuvant chemotherapy was allowed if the investigator determined that 1 of the 4 chemotherapy choices in the control arm would be an appropriate treatment option for the patient. Patients with prior platinum therapy for advanced disease were required to have no evidence of disease progression during platinum therapy. No prior treatment with a PARP inhibitor was permitted. Of the 431 patients randomized in the EMBRACA study, 408 (95%) were centrally confirmed to have a deleterious or suspected deleterious gBRCAm using a clinical trial assay; out of which 354 (82%) were confirmed using the BRACAnalysis CDx®. BRCA mutation status (breast cancer susceptibility gene 1 [BRCA1] positive or breast cancer susceptibility gene 2 [BRCA2] positive) was similar across both treatment arms.
The median age of patients treated with TALZENNA was 45 years (range 27 to 84) and 50 years (range 24 to 88) among patients treated with chemotherapy. Among all randomized patients, 1% versus 2% were males, 67% versus 75% were White; 11% versus 11% were Asian, and 4% versus 1% were Black or African American in the TALZENNA and chemotherapy arms, respectively. Almost all patients (98%) in both arms had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Approximately 56% of patients had estrogen receptor-positive and/or progesterone receptor-positive disease; 44% of patients had triple-negative disease, and the proportions were balanced across both treatment arms. Fifteen percent (15%) of patients in the TALZENNA arm and 14% of patients in the chemotherapy arm had a history of CNS metastases. Ninety-one percent (91%) of patients in the TALZENNA arm had received prior taxane therapy, and 85% had received prior anthracycline therapy in any setting. Sixteen percent (16%) of patients in the TALZENNA arm and 21% of patients in the chemotherapy arm had received prior platinum treatment in any setting. The median number of prior cytotoxic regimens for patients with advanced breast cancer was one; 38% received no prior cytotoxic regimens for advanced or metastatic disease, 37% received one, 20% received two, and 5% received three or more prior cytotoxic regimens.
The major efficacy outcome measure was progression-free survival (PFS) evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by blinded independent central review (BICR). A statistically significant improvement in PFS was demonstrated for TALZENNA compared with chemotherapy. A sensitivity analysis of investigator-assessed PFS was consistent with the BICR-assessed PFS results. Consistent PFS results were observed across patient subgroups defined by study stratification factors (line of therapy, TNBC status, and history of CNS metastases). The overall survival (OS) data were not mature at the time of the final PFS analysis (38% of patients had died). Efficacy data from the EMBRACA study are summarized in Table 5, and the Kaplan-Meier curves for PFS are shown in Figure 1.
|Abbreviations: BICR=blinded independent central review; CI=confidence interval.|
|Progression-Free Survival by BICR||N=287||N=144|
|Events, number (%)||186 (65)||83 (58)|
|Median months (95% CI)||8.6 (7.2, 9.3)||5.6 (4.2, 6.7)|
|Hazard Ratio (95% CI)*||0.54 (0.41, 0.71)|
|Patients with Measurable Disease by Investigator‡||N=219||N=114|
|Objective Response Rate, % (95% CI)§||50.2 (43.4, 57.0)||18.4 (11.8, 26.8)|
|Duration of Response Median¶ months (95% CI)||6.4 (5.4, 9.5)||3.9 (3.0, 7.6)|
Figure 1. Kaplan-Meier Curves of PFS – EMBRACA Study