Clinical trials results for PARP Inhibitors in ovarian cancer

Study Phase Patients (n) Setting Treatment arms Results P-value
Recurrent/relapsed setting
STUDY 42 [8] II 193 Recurrent pre-treaed advanced OC, BRCAmut Olaparib 400 mg BID (capsules) ORR: 34% MDR: 7.9 months
STUDY 19 [11] [12] II 265 Platinum-sensitive recurrent HGSOC Olaparib 400 mg BID (capsules)
Placebo
Overall population: 8.4 vs. 4.8 months P < 0.0001
BRCAmut: 11.2 vs. 4.3 months P < 0.0001
SOLO 2 [14] III 295 Platinum-sensitive recurrent HGSOC or HGEOC, BRCAmut Olaparib 300 mg BID
Placebo
Median PFS
19.1 vs. 5.5 months P < 0.0001
SOLO 3 [10] III 266 Platinum-sensitive recurrent HGSOC BRCAmut Olaparib 300 mg BID
Single-agent nonplatinum chemotherapy (weekly paclitaxel, weekly topotecan, gemcitabine or pegylated liposomal doxorubicin)
ORR: 72.2% vs. 51.4 P = 0.002
NOVA [15] III 553 Platinum-sensitive recurrent HGSOC Niraparib 300 mg
Placebo
Median PFS
gBRCAmut: 21 vs. 5.5 months P < 0.001
BRCAwt HRD+: 12.9 vs. 3.8 months P < 0.001
Overall non-gBRCA: 9.3 vs. 3.9 months P < 0.001
QUADRA [19] II 45 Platinum sensitive HRD positive HGSOC Niraparib 300 mg ORR: 27.5%
DCR: 68.6%
DoR: 9.2 months
STUDY 10 [21] I/II 42 Platinum-sensitive recurrent HGSOC or HGEOC, gBRCAmut (phase II PART 2A) Rucaparib 600 mg BID ORR: 59.5%
MDR: 7.8 months
ARIEL 2 PART 1 [22] II 192 Platinum sensitive recurrent HGSOC or HGEOC Rucaparib 600 mg BID Median PFS
BRCAmut: 12.8 months P < 0.0001
BRCAwt LOH High: 5.7 months P = 0.011
BRCAwt LOH low: 5.2 months P = 0.011
ARIEL 3 [24] III 564 Platinum-sensitive recurrent HGSOC or HGEOC Rucaparib 600 MG BID
Placebo
Median PFS
BRCAmut: 16.6 vs. 5.4 months P < 0.0001
HRD+: 13.6 vs. 5.4 months P < 0.0001
ITTP: 10.8 vs. 5.4 months P < 0.0001
Front-line
SOLO1 [30] III 391 FIGO Stage III/IV HGSOC or HGEOC BRCAmut Olaparib 300 mg BID
Placebo
BRCAmut:
> 36 (NR) vs. 13.8 months
P < 0.0001
HR: 0.30 (95% CI 0.23–0.41)
PAOLA-1 [31] III 806 FIGO Stage III/IV HGSOC or HGEOC Bevacizumab: 15 mg/kg, q21 × 15 months, including when administered with chemotherapy + olaparib (300 mg BID) × 24 months
Bevacizumab: 15 mg/kg, q21 × 15 months, including when administered with chemotherapy + Placebo × 24 months
Overall population ITT:
22.1 vs. 16.6 months
P < 0.0001
HR: 0.59 (95% CI 0.49–0.72)
BRCAmut:
37.2 vs. 21.7 months
HR: 0.31 (95% CI 0.20–0.47)
HRD (including BRCA):
37.2 months vs. 17.7 months
HR: 0.33 (95% CI 0.25–0.45)
HRD (BRCAwt):
28.1 months vs. 16.6 months
HR: 0.43 (95% CI 0.28–0.66)
HRP (BRCAwt):
16.9 months vs. 16.0
HR: 0.92 (95% CI 0.72–1.17)
PRIMA [32] III 733 FIGO Stage III with residual tumor IV HGSOC or HGEOC Niraparib 300 mg once daily, 36 months
Placebo once daily, 36 months
Overall population: 13.8 vs. 8.2 months P < 0.001
HR: 0.62 (95% CI 0.50–0.76)
BRCAmut: 22.1 vs. 10.9 months HR: 0.40 (95% CI 0.27–.62)
HRD (including BRCA): 21.9 vs. 10.4 months HR: 0.43 (95% CI 0.31–0.59)
HRD (BRCAwt): 19.6 vs. 8.2 months HR: 0.50 (95% CI 0.31–0.83)
HRP (BRCAwt): 8,1 vs. 5.4 months HR: 0.68 (95% CI 0.49–0.94)
VELIA [33] III 1140 FIGO Stage III/IV HGSOC Veliparib 150 BID in combination, 400 mg BID in maintenance Overall population:
23.5 vs. 17.3 months
P < 0.001
HR: 0.68 (95% CI 0.56–0.83)
BRCAmut: 34.7 vs. 22.0 months HR: 0.44 (95% CI 0.28–0.68)
HRD (including BRCA): 31.9 vs. 20.5 months HR: 0.57 (95% CI 0.43–0.76)
HRD (BRCAwt): 22.9 vs. 19.8 months HR: 0.74 (95% CI 0.52–1.06)
HRP (BRCAwt): 15.0 vs. 11.5 months HR: 0.81 (95% CI 0.6–1.09)

NR: not reached; wt: wild type