Intervention: Talazoparib
Trial phase: Phase 2
ATC code: L01XK04
SMILES: Cn1ncnc1[C@H]1c2n[nH]c(=O)c3cc(F)cc(c23)N[C@@H]1c1ccc(F)cc1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 61
Group description: During talazoparib treatment period, participants received oral administration of talazoparib 1 mg once daily (QD) for 24 weeks (6 cycles, 4 weeks per cycle), or 0.75 mg QD in case of moderate renal impairment at baseline, followed by definitive breast surgery within a maximum of 6 weeks of last dose.

Safety follow-up (end of treatment visit) occurred approximately 28 calendar days after the last dose of talazoparib or after permanent treatment discontinuation or before initiation of a new antineoplastic therapy (whichever occurred first).

Long-term follow-up was planned to be at least 3 years, which started from the date of surgery for event-free survival (EFS) and after first dose of talazoparib for overall survival (OS).
Eligibility criteria:
Inclusion Criteria:

Germline BRCA 1/2 Mutation Positive
Women and men at least 18 years of age or older.
Histologically confirmed invasive adenocarcinoma of the breast
HER2 negative breast cancer as defined by ASCO-CAP criteria
Tumor greater than or equal toT1, N0-3
No evidence of distant metastasis
Adequate bone marrow, hepatic, and renal function
ECOG performance status 0 or 1

Exclusion Criteria:

Any other previous antitumor therapies for the current cancer event. Treatment for ductal carcinoma in situ (DCIS) is allowed; ie, surgery, hormonal therapy and radiation.
Evidence of distant metastasis apparent prior to randomization
Patients with inflammatory breast carcinoma
Malignancy within the last 3 years, except: Stage 1 melanoma which does not require any further treatment after adequate surgical excision; adequately treated non melanoma skin cancer; Curatively treated in situ cancer of the cervix; Stage 1, Grade 1 endometrial carcinoma; or Adequately treated contralateral breast carcinoma which has been disease free for a year; Other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for 5 years.
Previous or concomitant systemic anti cancer therapies used for the treatment of cancer in the last 3 years.
Prior treatment with a PARP inhibitor in any disease setting
Concomitant use of Strong P gp inhibitors or inducers or BCRP inhibitors
Patients who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol
Major surgery within 14 days prior to study entry
Known history of cardiac disease, for example : Myocardial infarction or symptomatic cardiac ischemia within 24 weeks before screening; Congestive heart failure New York Heart Association Class III or IV; History of clinically significant ventricular arrhythmias within one year prior to randomization; History of Mobitz II second degree or third degree heart block, uncontrolled hypertension.
Active clinically significant infection
Clinically significant bleeding diathesis or coagulopathy
Non healing wound, ulcer or bone fracture
Known hypersensitivity to any of the components of talazoparib
Patients with myelodysplastic syndrome/acute myeloid leukemia
Patients with uncontrolled seizures.
Any evidence of other disease or any concomitant medical or psychiatric problems which in the opinion of the Investigator would prevent completion of treatment