The drug combination of niraparib (ZEJULA) and pembrolizumab (KEYTRUDA) shows promising antitumor activity in patients with advanced metastatic triple-negative breast cancer (TNBC), according to a study published in JAMA Oncology.
In this open-label, single-arm, phase II study, researchers recruited 55 patients with advanced or metastatic TNBC regardless of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression from 34 locations across the US. Following enrollment, patients were administered 200 mg of niraparib orally once daily in conjunction with 200 mg of intravenous pembrolizumab on day one of a series of 21-day cycles. The primary outcome in this study was the objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors, version one. Secondary outcomes included safety, disease control rate (DCR; complete response plus partial response plus stable disease), duration of response (DOR), progression-free survival (PFS), and overall survival. The researchers aggregated data from January 3, 2017 through October 29, 2018 and analyzed the data from October 29, 2018 through February 27, 2019.
Combo of PARP inhibitor niraparib w pembrolizumab immunotherapy in pts w adv triple-negative #BreastCancer led to objective response rate (ORR) 21%, notably ORR 47% among pts w BRAC mutation on single arm ph 2 trial https://t.co/z5rmzX3F6k #BCSM
— JAMA Oncology (@JAMAOnc) June 13, 2019
Combination Exhibits Efficacy
According to the study results, five patients had confirmed complete responses, five more had confirmed partial responses, 13 had stable disease, and 24 had progressive disease. Additional, in the efficacy-evaluable population (n = 47), ORR comprised 10 patients (21%; 90% CI, 12% to 33%) and DCR included 23 patients (49%; 90% CI, 36% to 62%). The results further showed that median DOR was not reached at the time of the data cutoff, with seven patients still receiving treatment at the time of analysis.
Moreover, 15 evaluable patients with tumor BRCA mutations, ORR comprised seven patients (47%; 90% CI, 24%-70%), DCR included 12 patients (80%; 90% CI, 56%-94%), with a median PFS of 8.3 months (95% CI, 2.1 months to not estimable). Further, 27 evaluable patients with BRCA wild-type tumors, ORR included 3 patients (11%; 90% CI, 3%-26%), DCR included 9 (33%; 90% CI, 19%-51%), and median PFS was 2.1 months (95% CI, 1.4-2.5 months).
“Of particular importance is that the combination treatment demonstrated clinical activity in patients irrespective of BRCA mutation or PD-L1 status, although the clinical activity is more pronounced in patients with tBRCAmut or those with PD-L1–positive tumors”, the study researchers wrote.
“These data suggest that the combination of a PARP inhibitor and an anti–PD-1 antibody has a tolerable safety profile in patients with advanced or metastatic TNBC and promising antitumor activity, irrespective of BRCA mutation status,” the researchers continued. “To confirm the findings of this trial, further clinical development of niraparib in combination with PD-1 inhibition in larger-scale studies is under consideration.”
Niraparib (PARPi) + pembro for metastatic #tnbc:
-Of 55pts, 10 with complete/partial response
-49% disease control rate.
-Most benefit was in BRCAmut patients
— Daniel Stover, MD (@StoverLab) June 14, 2019