Talazoparib has shown clinical efficacy in breast cancer patients with germline BRCA1 or BRCA2 mutations. Beyond BRCA1 and BRCA2 mutations, it is plausible that talazoparib may have activity in patients with homologous recombination defects (HRD).
BRCA 1/2 plays an essential role in homologous recombination repair and breast cancer patients with BRCA 1/2 germline mutation have homologous recombination defects (HRD). Besides BRCA1 or BRCA2 germline mutation, a proportion of breast cancer is characterized as having HRD through germline mutation, somatic mutation, and epigenetic alteration of other homologous recombination repair (HRR) genes (which includes but are not limited to ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L) (5). It is speculated that tumor with HRD may have clinical benefit from PARP inhibitor. However, the efficacy of talazoparib in advanced breast cancer with HRD is not known. The primary purpose of the present study is to evaluate the efficacy of talazoparib in breast cancer with HRD.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
70
\- Patients will receive Talazoparib 1 mg orally once daily continuously, with or without food. Laboratory values will be monitored every 4 weeks until progression or unacceptable toxicity. Dose modifications should be made based on the observed toxicity
Seoul National University Hospital
Seoul, South Korea
RECRUITINGResponse rate (RR)
Defined as a complete response (CR) or partial response (PR) on two consecutive assessments, at least 28 days apart, as determined by investigator assessment using RECIST v1.1
Time frame: Enrollment to end of treatment up to 2 years
Progression-free survival (PFS)
Defined as the time from the date of first dose administration to the first occurrence of disease progression, as determined by investigator assessment using RECIST v1.1, or death from any cause, whichever occurs first.
Time frame: First day of study treatment to the date of disease progression or death due to any cause, whichever came first, assessed up to 2 years
Duration of objective response (DOR)
Defined as the time from first occurrence of a documented objective response to disease progression, as determined by investigator assessment using RECIST v1.1 or death from any cause, whichever occurs first
Time frame: Enrollment to end of treatment up to 2 years
Clinical benefit rate (CBR)
Defined as having received CR or PR of any duration or stable disease (SD) ≥ 3 months per RECIST v1.1;
Time frame: Enrollment to end of treatment up to 2 years
Overall survival (OS)
Defined as the time from the date of first dose administration to death from any cause
Time frame: First day of study treatment to the date of death due to any cause, assessed up to 2 years
Safety profile (Treatment-related adverse events as assessed by CTCAE v4.0)
Number of participants with treatment-related adverse events will be assessed
Time frame: First day of study treatment to end of treatment, assessed up to 2 years
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