Table 2 Clinical trials on PARP inhibitor maintenance treatment in EOC (recurrent and frontline)

 Study-19 [52, 53]

Randomised, double-blind, phase II study

≥2 prior lines of chemotherapy HGSOC platinum-sensitive

Olaparib 400 mg BID capsules (n = 136) versus placebo (n = 129)

mPFS:

▪ BRCA mutation: 11.2 vs. 4.3 (HR: 0.18, 0.10–0.31)

▪ BRCAwt: 7.4 vs. 5.5 (HR: 0.54, 0.34–0.85, p = 0.0075)

▪ ITT: 8.4 vs. 4.8 (HR: 0.35, 0.25–0.49, p < 0.001)

mOS:

▪ At the second interim analyses, OS did not significantly differ between the groups (HR: 0·88, 0.64–1.21, p = 0.44); similar findings were noted for patients with mutated BRCA

▪ In the ITT population PFS benefit was seen irrespective of BRCA, Also patients with BRCA mutation have the greatest likelihood of benefit from olaparib therapy.

 NOVA [26, 27]

Randomised, double-blind, phase III trial

≥2 prior lines of chemotherapy High-grade serous platinum-sensitive HRD testing in BRCAwt

Niraparib 300 mg OD (n = 372) versus placebo (n = 181)

mPFS:

▪ BRCA mutation: 21.0 vs. 5.5 (HR: 0.27, 0.17–0.41)

▪ BRCAwt, HRD: 12.9 months) (HR: 0.38, 0.24–0.59)

▪ BRCA cohort (9.3 months) (HR: 0.45, 0.34–0.61, p < 0.001 for all three comparisons)

mPFS2:

BRCA mutation: HR: 0.67 (0.48 − 0.95)

BRCAwt: 0.81 (0.62 − 1.05)

mOS: Restricted mean survival time analyses up to 72 months

BRCA mutation: 45.9 vs 43.2 (Δ of 2.7 m,: − 4.1 − 9.5)

BRCAwt: 38.5 vs 39.1 (Δ of − 0.6 m, − 6.0 − 4.7)

▪ The mPFS duration was significantly longer among those who received niraparib regardless of the presence or absence of gBRCA mutations/HRD status, with moderate bone marrow toxicity.

▪ The final data support the safe long-term use of niraparib for maintenance treatment. PFS2 analyses indicates that the benefit of niraparib maintenance therapy extends beyond first progression. The NOVA study was not powered for OS and analyses is confounded by a high rate of crossover and missing data thus limiting its interpretation.

 ARIEL-3 [23]

Randomised, double-blind, placebo-controlled, phase III trial

≥2 prior lines of chemotherapy High-grade serous or endometrioid platinum-sensitive

Rucaparib 600 mg BID (n = 375) versus placebo (n = 189)

mPFS:

▪ BRCA mutation: 16.6 vs. 5.4 (13.4–22.9, p < 0·0001)

▪ HRD: 13·6 vs. 5.4 (10.9–16.2, p < 0·0001)

▪ ITT population: 10.8 vs. 5.4 (8.3–11.4, p < 0·0001)

▪ Across all primary analyses groups (BRCA mutant carcinoma, HRD carcinoma and ITT population), rucaparib substantially improved PFS in patients with platinum-sensitive OC who had achieved a response to platinum-based chemotherapy.

 SOLO-2 [24, 25]

Multicentre, double-blind, randomised, placebo-controlled, phase III trial

≥2 prior lines of chemotherapy high-grade serous or endometrioid platinum-sensitive gBRCA mutations

Olaparib 300 mg bd tablets (n = 196) verses placebo (n = 99)

mPFS:

BRCA mutation: Investigator-assessed mPFS: 19.1 vs. 5.5 (HR: 0.30, 0.22–0.41, p < 0.001)

mOS:

▪ A long-term treatment benefit was seen with olaparib vs placebo (51.7 vs. 38.8) with an HR of 0.74 (0.54–1.00, p = 0·054)

▪ Maintenance olaparib provided an unprecedented improvement of 12.9 months in median OS vs placebo in patients with platinum-sensitive, relapsed OC with BRCA mutation.

 SOLO-1 [54]

Randomised, double-blind, phase III trial

Stage III/IV HGSOC or endometrioid g BRCA mutations CR or PR to chemotherapy

Olaparib 300 mg BID tablets (n = 260), vs. placebo (n = 131)

mPFS:

▪ After 5 years: 56 vs. 13.8 (HR: 0.33 0.25–0.43)

▪ The use of maintenance therapy with olaparib provided a substantial benefit with regard to PFS with a 63% lower risk of disease progression or death with olaparib than with placebo.

▪ After 5-years, almost half of patients receiving maintenance olaparib were progression-free compared to with placebo (20%). Over 50% of patients in complete response after first-line platinum-based chemotherapy remained free from relapse 5 years later.

 PRIMA [55]

Randomised, double-blind, phase III trial

Stage III (residual disease)/IV HGSOC or endometrioid CR or PR to chemotherapy

Niraparib 300 mg (n = 487) vs. placebo (n = 246)

mPFS:

▪ ITT: 13.8 vs. 8.2 (HR: 0.62, 0.50–0.76, p < 0.001)

▪ HRD: 21.9 vs. 10.4 (HR: 0.43, 0.31–0.59, p < 0.001)

▪ BRCA mutation: 22.1 vs. 10.9 (HR: 0.40, 0.27–0.62)

▪ BRCAwt, HRD: 19.6 vs. 8.2 (HR: 0.50, 0.31–0.83)

mOS:

▪ At the 24-month interim analyses, the rate of OS in the niraparib group was 84%

▪ Among patients with newly diagnosed advanced OC who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer PFS, regardless of the presence or absence of HRD.

 VELIA [57]

Phase III, placebo-controlled trial

Stage III/IV HGSOC CR, PR or SD to chemotherapy

Carboplatin/taxane plus maintenance placebo (n = 375), carboplatin/taxane and maintenance veliparib (n = 383) vs. carboplatin/taxane with veliparib and maintenance veliparib (n = 382)

mPFS:

▪ ITT population: 23.5 vs. 17.3 (HR: 0.68, 0.56–0.83, p < 0.001)

▪ BRCA mutation: 34.7 vs. 22.0 (HR: 0.44, 0.28–0.68, p < 0.001)

▪ HRD: 31.9 vs.20.5 (HR: 0.57, 0.43–0.76, p < 0.001)

▪ BRCAwt and HRD: 15.0 vs. 11.5 (HR: 0.74, 0.52–0.76)

▪ BRCAwt: 18.2 vs. 15.1 (HR: 0.80, 0.64 –1.00)

▪ Across all study populations, treatment with carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer PFS than carboplatin plus paclitaxel induction therapy alone.

 PAOLA-1 [56]

Randomised, double-blind, phase III trial

Stage III/IV high-grade serous or non-serous OC with CR or PR to chemotherapy

Olaparib 300 mg (n = 537) BID plus bevacizumab (15 mg/kg dL, q3w) versus placebo (n = 269) plus bevacizumab

mPFS:

▪ ITT population: 22.1 vs. 16.6 (HR: 0.59, 0.49 –0.72, p < 0.001)

▪ BRCA mutation cohort: 37.2 vs 21.7 (HR: 031, 0.20–0.47)

▪ HRD: 37.2 vs. 17.7 (HR:0.33, 0.25–0.45)

▪ BRCAwt and HRD: 28.1 vs. 16.6 (HR: 0.43, 0.28–0.66)

▪ BRCAwt: 18.9 vs. 16.0 (HR: 0.71, 0.58–0.88)

▪ In patients with advanced OC receiving first-line therapy with bevacizumab, the addition of maintenance olaparib provided a substantial PFS benefit, which was significant in patients with HRD-positive tumours, including individuals without a BRCA mutation.