Table 2.

Different PARP Inhibitors Comparison and Summarized Clinical Benefits

PARP Inhibitors	Olaparib	Rucaparib	Niraparib	Talazoparib	Veliparib	Pamiparib	Fluzoparib
IC50 (nM)	1	1	4	0.6	2	0.83	1.5
Targets	PARP1/2/3/4	PARP1/2/3/4, TNKS1	PARP1/2	PARP1/2	PARP1/2/3	PARP1/2	PARP1/2
Trapping capacity [1–5]	++	++	++	+++	-	++	N.A.
Single-agent dose	300 mg PO BID	600 mg PO BID	300 mg PO BID	1 mg PO QD	400 mg PO BID	60 mg PO BID	N.A.
CNS penetration	+	+	++	-	+	++	N.A.
T1/2 (hours)	11.9	25.9	48–51	90 ± 58	4.1–8.2	N.A.	N.A.
P-glycoprotein substrate	Yes	Yes	Weak	Weak	No	No	N.A.
Off-target interactions	CYP3A4	CYP enzymes	Dopamine, norepinephrine and serotonin transporters	None	N.A.	N.A.	N.A.
Toxicities (most frequent)	Nausea, fatigue, vomiting, diarrhea, dysgeusia, headache	Nausea, fatigue, vomiting, diarrhea, dysgeusia, LFT elevation	Nausea, fatigue, LFT elevation, vomiting, headache, insomnia, HTN	Nausea, fatigue, headache, vomiting, alopecia, diarrhea	Nausea, fatigue, lymphopenia	Nausea, fatigue	Limited early-phase trial data
Grade higher than 3 hematologic toxicities	Anemia, neutropenia	Anemia, neutropenia	Thrombocytopenia, anemia, neutropenia	Anemia, neutropenia, thrombocytopenia	NTD	Anemia, neutropenia	NTD
Clinical benefits	SOLO1 (ovarian maintenance), HR 0.30, PFS benefit; SOLO2 (relapsed ovarian maintenance), HR 0.30, PFS benefit; OympiAD (HER2 BC), HR 0.58, PFS benefit	ARIEL2 (relapsed ovarian), HR 0.27, PFS benefit; ARIEL3 (relapsed ovarian maintenance), HR 0.23, PFS benefit	NOVA (relapsed ovarian maintenance), HR 0.27, PFS benefit	EMBRACA (HER2 BC), HR 0.54, PFS benefit	BROCADE 3 (advanced BC), HR, 0.71, PFS benefit	Ongoing, data not mature (NCT03427814)	NTD
Approvals	Ovarian, Breast	Ovarian	Ovarian	Breast (FDA)	NTD	NTD	NTD

CNS, central nervous system; CYP, cytochrome P450; IC50, half maximal inhibitory concentration; N.A., not available; PARP, poly(ADP-ribose) polymerase; TNKS1, tankyrase 1; -, poor; +, modest; ++, good; HR, hazard ratio; PFS, progression-free survival