On October 16, 2018, the FDA approved poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib (Talzenna®, Pfizer) for use in patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Patients should be selected for the PARP inhibitor (PARPi)-treatment using the FDA-approved companion diagnostic (CDx) for talazoparib.

EMBRACA Trial

The Phase III, open‑label, parallel-arm, multi-centre EMBRACA (NCT01945775) study randomised 431 patients with gBRCAm HER2‑negative locally advanced or metastatic breast cancer in a 2:1 fashion to either receive talazoparib (1 mg) or physician’s choice chemotherapy (i.e. capecitabine, eribulin, gemcitabine, or vinorelbine). All participants had a known or suspected deleterious gBRCA mutation and received ≤3 lines of prior cytotoxic systemic therapies for locally advanced or metastatic disease. All patients had received prior treatment with an anthracycline and/or a taxane —unless contraindicated— in the (neo)adjuvant and/or metastatic treatment setting. The primary efficacy endpoint was progression-free survival (PFS) by blinded independent central review (BIRC) according to RECIST1.1.

The estimated median PFS in the talazoparib-arm was 8.6 months vs 5.6 months in the chemotherapy-arm (HR 0.54; 95% CI, 0.41-0.71; p<0.0001).

Safety

The most common (≥20%) adverse reactions of any Grade were fatigue, anaemia, nausea, neutropenia, headache, thrombocytopenia, vomiting, alopecia, diarrhoea, and decreased appetite. The FDA approved prescribing information contains warnings and precautions for myelodysplastic syndrome/acute myeloid leukaemia, myelosuppression, and embryo-foetal toxicity.

Companion Diagnostic

Together with the approval of talazoparib, the FDA approved the BRACAnalysis CDx test (Myriad Genetic Laboratories, Inc.) to identify (suspected) deleterious gBRCAm and to select breast cancer patients eligible for talazoparib-treatment. The BRACAnalysis CDx test was validated in the EMBRACA trial population.

Prescribing information Talzenna.