Table 4 Clinical trials of niraparib for cancer patient with different histological subtypes

Hundred patients with advanced solid tumors in three sites ((dose escalation study)

phase I

Two cohort studies with single arm in each

Part A: 60 patients

 • enriched for BRCA1 and BRCA2 mutation carriers

 • received niraparib daily at ten escalating doses from 30 mg to 400 mg in a 21-day cycle to establish the maximum tolerated dose

Part B: 40 patients

 • sporadic platinum-resistant HGSOC and sporadic prostate cancer

 • investigating the maximum tolerated dose

- maximum tolerated dose is 300 mg/day dose liming toxic effects (Initial cycle)

- Grade 3 fatigue (30 mg/day) and pnemonitis (60 mg/day) were observed during first cycle

- Grade 4 thrombocytopenia (400 mg/day)

- Other common treatment related grade 1 and 2 side effects

- Inhibition of PARP exceeds 50% at dose greater than 80 mg/day (80 mg > ED50)

- Antitumor effect was observed beyond 60 mg/day

[54]

Patients with sporadic CRPC

Phase I

randomized clinical trial with two treatment arms (21 patients)

‑ Arm 1: niraparib 290–300 mg/day

‑ Arm 2: placebo

- Stabilization of CRPC

- in 43% of patients with a median duration of response of 254 days

- 30% of patients had a decrease of circulating tumor cells

- No correlation between ERG rearrangements/loss of PTEN expression and treatment response.

[55]

Patients with recurrent OC (553 patients)

phase III

Randomized double blind clinical trial with two category ad two arms per category

- Arm 1: Niraparib 300 mg once daily

 • 138 patients

- Arm 2: placebo

 • 65 patients

➢ Both arm 1 and 2 patients are with gBRCA mutant tumors

- Arm 3: Niraparib 300 mg once daily

 • 234 patients

- Arm 4: Placebo

 • 116 patients

➢ Both arm 3 and 4 patients are with non-gBRCA mutant (wild type) tumors irrespective of HR status

The primary outcomes were PFS

In gBRCA cohort

 • (21 months vs. 5.5 months for treatment to placebo)

For non-gBRCA cohort with HRD positivity

 • The PFS was found to be 12.9 and 3.8 months for niraparib and placebo arms, respectively.

Overall PFS in non-gBRCa cohor

 • 9.3 months vs 3.9 months

[56]

181 patients with recurrent OC, no prior use PARP inhibitors and at least 2 previous platinum therapy

Phase III

Randomized double blind clinical trial (two cohorts based on gBRCA status)

Platinum resistance rates were 42%, 53% and 49% for gBRCA, non-gBRCA and pooled cohorts, respectively

[57]