PARP inhibitors 

PARP inhibitors are a type of targeted therapy that work by blocking a protein used to repair damaged DNA. They were initially developed to treat cancers in people with an inherited BRCA1 or BRCA2 mutation. Since then, research and additional FDA approvals have expanded use of PARP inhibitors to more people and situations. There are four PARP inhibitors that have received FDA approval for treating different types of advanced cancers. 

Indications vary by:

• type and stage of cancer: currently PARP inhibitors have been approved to treat breast, ovarian, pancreatic and prostate cancers. 
• presence of a mutation or biomarker: PARP inhibitor have been approved in different settings for:  
  • people with certain inherited mutations.
  • people with certain acquired mutations.
  • people with certain tumor biomarkers.
  • women with certain types of ovarian cancer, regardless of inherited mutation or biomarker status.
• number of and response to prior treatments: PARP inhibitor have been approved in different settings for:
  • platinum-sensitive or partially platinum sensitive ovarian cancer. 
  • metastatic, castration-resistant prostate cancer (mCRPC).
  • after chemotherapy. 
  • to treat progression or recurrence after a specific number of prior treatments. 

Clinical trials studying PARP inhibitors in new settings or combinations are enrolling patients. As research continues, these approvals may expand to include treatment for additional cancers, earlier stages of cancer, people with other inherited mutations, and based on different tumor biomarkers.

 

 Indications for PARP inhibitors

Cancer type	Indication	Biomarker or inherited  mutation	PARP inhibitor
			Lynparza olaparib	Rubraca rucaparib	Talzenna  talazoparib	Zejula niraparib
Metastatic breast cancer	For treatment of patients who have previously received chemotherapy, or hormone therapy for patients with hormone receptor (HR)-positive disease	Inherited BRCA1 or BRCA2 mutation and Her2-negative	X
Metastatic breast cancer	For treatment of metastatic breast cancer	Inherited BRCA1 or BRCA2 mutation and Her2-negative			X
Early stage breast cancer at high risk for recurrence	Maintenance therapy after chemotherapy in people with an inherited BRCA1 or BRCA2 mutation. Although the FDA has not yet approved this indication, several expert guidelines (including NCCN) now recommend this treatment option.	Inherited BRCA1 or BRCA2 mutation and Her2-negative	X
Stage 2-4 ovarian, fallopian tube or primary peritoneal  cancer	First-line, maintenance therapy for women who had a complete or partial response to platinum chemotherapy	Homologous Recombination Deficiency  (HRD) testing	X (combined with Avastin)
Stage 2-4 ovarian, fallopian tube, or primary peritoneal  cancer	First-line maintenance therapy for women who had a complete or partial response to platinum chemotherapy	Inherited or acquired (tumor) mutation in BRCA1 or BRCA2	X
Stage 2-4 ovarian, fallopian tube, or primary peritoneal  cancer	First-line maintenance women who had a complete or partial response to platinum chemotherapy	No inherited or acquired mutation or other tumor biomarker needed				X
Recurrent ovarian,  fallopian tube or primary peritoneal cancer	Second-line (or later) maintenance therapy for platinum-sensitive or partially sensitive cancer	No inherited or acquired mutation or other tumor biomarker needed	X	X		X
Metastatic pancreatic cancer	First-line maintenance therapy for patients whose disease has not progressed on at least 16 weeks of  platinum-based chemotherapy	Inherited mutation in BRCA1 or BRCA2	X
Metastatic castration-resistant prostate cancer (mCRPC)	Men with mCRPC whose cancer has progressed following treatment with Xtandi (enzalutamide) or  Zytiga (abiraterone)	Inherited mutation in BRCA1 or BRCA2 or tumor mutation one of the following genes:  ATM, BRCA1, BRCA2, BARD1, BRIP1, CDK12, CHEK2, FANCL, PALB2, RAD51B, RAD51C,  RAD51D ,  RAD54	X
Metastatic castration-resistant prostate cancer (mCRPC)	Men with mCRPC who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy	Inherited or acquired (tumor) mutation in BRCA1 or BRCA2		X