A randomized phase II clinical trial of talazoparib maintenance therapy in triple-negative breast cancer patients who showed platinum-sensitivity on first- or second-line platinum-based chemotherapy (KCSG BR21-10)

초록

Background: A potent PARP inhibitor, talazoparib, demonstrated superior clinical activity compared to standard chemotherapy in BRCA1/2-mutant advanced breast cancer patients. However, the role of talazoparib treatment in BRCA1/2 wild-type triple-negative breast cancer (TNBC) patients remains undefined, although high incidence of homologous recombination deficiency (HRD) is one of the major characteristics of the TNBC. Previous studies indicated clinical responsiveness to platinum agents is a useful surrogate for HRD that may predict favorable PARP inhibitor response. Here, we present a phase II study to test talazoparib maintenance therapy in BRCA1/2 mutation unselected advanced TNBC patients after platinum-based chemotherapy. Methods: The KCSG BR21-10 study (NCT04755868) is a randomized double-blind placebo-controlled phase II clinical trial of talazoparib maintenance therapy in metastatic TNBC patients whose tumor showed platinum-sensitivity to first- or second-line platinum-based chemotherapy. The criteria for platinum-sensitivity was set as follows: remaining complete response (CR), partial response (PR), or stable disease (SD) after 6 to 9 tri-weekly doses or 18 to 27 weekly doses of platinum-based chemotherapy. The eligible TNBC patients are enrolled to the trial after completion of platinum-based therapy and 1:1 randomized to receive talazoparib (once daily 1.0 mg) or placebo maintenance therapy. The patient with any germline BRCA1/2 mutation status is eligible (with or without pathogenic mutation), and randomization stratification factors include line of platinum-based chemotherapy (1st versus 2nd line), response to platinum-based chemotherapy (CR/PR versus SD), and germline BRCA1/2 mutation status. Patients are excluded if their disease showed progression at any time point after start of platinum-based chemotherapy. The talazoparib/placebo maintenance treatment is initiated within 8 weeks after the last platinum chemotherapy and continues until d