Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial

Carolyn Vachani, RN, MSN, AOCN
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 3, 2009

Title: Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin (G/C) in patients with metastatic triple-negative breast cancer (TNBC): Results of a randomized phase II trial
Reviewer: Arpi Thukral, MD
Presenter: Joyce O'Shaughnessy, MD
Affiliation: US Oncology Group

PARP is an enzyme that allows cells to repair themselves after they've been damaged. It is increased in the majority of triple negative breast cancers (TNBC), causing them to be more aggressive and resistant to therapy. The inhibition of PARP is a strategy that has been shown to have success in BRCA 1 & 2 related breast cancers. BSI-201 is a PARP1 inhibitor that was used in this trial for the treatment of metastatic TNBC.

One-hundred and twenty-three participants enrolled with metastatic TNBC and having received 2 or fewer different chemotherapy regimens. They received gemcitabine and carboplatin with or without BSI-201. The group receiving BSI-201 faired better in all areas being studied (see below). There were no statistically significant differences seen in toxicities between the 2 groups.

	Control group (GC alone)	GC +BSI-201 group	p-value
CBR*	21%	62%	p=0.0002
Objective tumor response rate**	16%	48%	p=0.002
Median PFS	3.1 months	6.9 months	p<0.0001
Median OS	5.7 months	9.2 months	p=0.0005

*CBR = All Complete responders + All Partial responders + those with stable disease for >6 months; so basically all who derived any benefit from the treatment

** Objective tumor response rate= all complete and partial responders

***Any p value less than 0.05 is considered statistically significant;the lower the value, the more significant.

This was a relatively small study, but given the promising results, a phase III trial is planned to open this summer. Further study of this agent and other PARP inhibtors will help us determine its therapeutic potential not only in triple- negative breast cancer, but possibly in other cancer types as well.

Also see Interpreting a Cancer Research Study