Talazoparib

The EMBRACA trial (NCT01945775) was a randomized, open label, phase III trial that assigned 431 patients with germline BRCA1 or BRCA2 pathogenic variants and locally advanced or metastatic breast cancer in a 2:1 ratio to talazoparib (1 mg PO qd) or standard single-agent chemotherapy of the physician’s choice (eribulin, capecitabine, gemcitabine, or vinorelbine).[87] All patients had received previous treatment with an anthracycline, taxane, or both. Patients had received three or fewer lines of cytotoxic chemotherapy for advanced breast cancer. Previous platinum therapy in the setting of early breast cancer was permitted if it was completed at least 6 months before progressive disease or if there was no objective progression while on platinum therapy in the advanced-disease setting. Hormone receptor–positive and hormone receptor–negative patients were enrolled.

The EMBRACA trial (NCT01945775) was a randomized, open label, phase III trial that assigned 431 patients with germline BRCA1 or BRCA2 pathogenic variants and locally advanced or metastatic breast cancer in a 2:1 ratio to talazoparib (1 mg PO qd) or standard single-agent chemotherapy of the physician’s choice (eribulin, capecitabine, gemcitabine, or vinorelbine).[87] All patients had received previous treatment with an anthracycline, taxane, or both. Patients had received three or fewer lines of cytotoxic chemotherapy for advanced breast cancer. Previous platinum therapy in the setting of early breast cancer was permitted if it was completed at least 6 months before progressive disease or if there was no objective progression while on platinum therapy in the advanced-disease setting. Hormone receptor–positive and hormone receptor–negative patients were enrolled.

Median PFS was significantly longer in the talazoparib group than in the standard therapy group (8.6 months vs. 5.6 months; HRdisease progression or death, 0.54; 95% CI, 0.41–0.71; P < .001).

The EMBRACA trial (NCT01945775) was a randomized, open label, phase III trial that assigned 431 patients with germline BRCA1 or BRCA2 pathogenic variants and locally advanced or metastatic breast cancer in a 2:1 ratio to talazoparib (1 mg PO qd) or standard single-agent chemotherapy of the physician’s choice (eribulin, capecitabine, gemcitabine, or vinorelbine).[87] All patients had received previous treatment with an anthracycline, taxane, or both. Patients had received three or fewer lines of cytotoxic chemotherapy for advanced breast cancer. Previous platinum therapy in the setting of early breast cancer was permitted if it was completed at least 6 months before progressive disease or if there was no objective progression while on platinum therapy in the advanced-disease setting. Hormone receptor–positive and hormone receptor–negative patients were enrolled.

Benefits were observed in all subgroups, although CIs were wide in the subgroup of patients who had received previous platinum therapy.

The EMBRACA trial (NCT01945775) was a randomized, open label, phase III trial that assigned 431 patients with germline BRCA1 or BRCA2 pathogenic variants and locally advanced or metastatic breast cancer in a 2:1 ratio to talazoparib (1 mg PO qd) or standard single-agent chemotherapy of the physician’s choice (eribulin, capecitabine, gemcitabine, or vinorelbine).[87] All patients had received previous treatment with an anthracycline, taxane, or both. Patients had received three or fewer lines of cytotoxic chemotherapy for advanced breast cancer. Previous platinum therapy in the setting of early breast cancer was permitted if it was completed at least 6 months before progressive disease or if there was no objective progression while on platinum therapy in the advanced-disease setting. Hormone receptor–positive and hormone receptor–negative patients were enrolled.

Median OS did not differ between the two groups (22.3 months vs. 19.5 months; HRdeath, 0.76; 95% CI, 0.55–1.06; P = .11), although survival data are not yet mature.

The EMBRACA trial (NCT01945775) was a randomized, open label, phase III trial that assigned 431 patients with germline BRCA1 or BRCA2 pathogenic variants and locally advanced or metastatic breast cancer in a 2:1 ratio to talazoparib (1 mg PO qd) or standard single-agent chemotherapy of the physician’s choice (eribulin, capecitabine, gemcitabine, or vinorelbine).[87] All patients had received previous treatment with an anthracycline, taxane, or both. Patients had received three or fewer lines of cytotoxic chemotherapy for advanced breast cancer. Previous platinum therapy in the setting of early breast cancer was permitted if it was completed at least 6 months before progressive disease or if there was no objective progression while on platinum therapy in the advanced-disease setting. Hormone receptor–positive and hormone receptor–negative patients were enrolled.

The primary toxicity observed with talazoparib was myelosuppression, especially anemia.

The EMBRACA trial (NCT01945775) was a randomized, open label, phase III trial that assigned 431 patients with germline BRCA1 or BRCA2 pathogenic variants and locally advanced or metastatic breast cancer in a 2:1 ratio to talazoparib (1 mg PO qd) or standard single-agent chemotherapy of the physician’s choice (eribulin, capecitabine, gemcitabine, or vinorelbine).[87] All patients had received previous treatment with an anthracycline, taxane, or both. Patients had received three or fewer lines of cytotoxic chemotherapy for advanced breast cancer. Previous platinum therapy in the setting of early breast cancer was permitted if it was completed at least 6 months before progressive disease or if there was no objective progression while on platinum therapy in the advanced-disease setting. Hormone receptor–positive and hormone receptor–negative patients were enrolled.

Patient-reported outcome data demonstrated more favorable effects of talazoparib than standard chemotherapy on quality-of-life measures.[88]