Abstract 1955
Background
Niraparib is a highly selective PARP-1/-2 inhibitor approved by FDA for the maintenance therapy of platinum-sensitive recurrent (PSR) ovarian cancer based on the significantly improved progression-free survival for niraparib-treated patients (pts) in the phase III NOVA study. A retrospective analysis of NOVA study suggests that pts with BW <77 kg or baseline plt count <150*109/L may have an improved safety profile from a starting dose of 200 mg once daily (QD) without compromising efficacy. A double-blinded, 2:1 randomized, placebo-controlled phase III study (NORA) is being conducted in China to investigate niraparib as maintenance therapy in Chinese pts with PSR ovarian cancer. The dosing regimen in the study was 300 mg QD but the study protocol was subsequently amended to have a starting dose of either 300 or 200 mg of niraparib/placebo QD based on baseline BW and plt counts. The trial has completed accrual and remains blinded for efficacy and safety. The current analysis was intended to evaluate niraparib tolerability for pts starting treatment with an individualized starting dose and compare with that in pts with the fixed starting dose of 300 mg QD.
Methods
The initial protocol adopted a fixed starting dose of 300 mg QD. After 16 patients were enrolled, the protocol was amended to start niraparib treatment at a dose of 200 mg QD in pts with BW <77 kg or plt count <150*109/L, and 300 mg for others. Blinded data were pooled from niraparib and placebo arms.
Results
A total of 265 pts had been enrolled, and 232 pts who have been followed up ≥ 90 days ending Mar 31, 2019 were included in this analysis. There were no major differences in key pts demographics or disease characteristics between both arms. Key safety data are presented in the table. More detailed safety data in all population will be disclosed.Table: 1004P
| Pre-Amendment, Fixed starting dose (pooled niraparib and placebo arms) | Post-Amendment, Individualized starting dose (pooled niraparib and placebo arms ) | |||
|---|---|---|---|---|
| 300 mg (N = 16) | 300 mg (N = 14) | 200 mg (N = 202) | Total (N = 216) | |
| Median BW, kg (min, max) | 62 (40,76) | 83 (78,94) | 59 (37,82) | 61 (37,94) |
| Median plt count,109/L (min, max) | 211 (124,336) | 187(153,325) | 184 (62,447) | 184 (62,447) |
| Any ≥ grade 3 TEAE, n(%) | 9 (56.3) | 4 (28.6) | 56 (27.7) | 60 (27.8) |
| ≥Grade 3 thrombocytopenia, n(%) | 3 (13.8) | 1 (7.1) | 6 (3.0) | 7 (3.2) |
| ≥Grade 3 anemia, n(%) | 4 (25.0) | 2 (14.3) | 9 (4.5) | 11 (5.1) |
| ≥Grade 3 neutropenia, n(%) | 2 (12.5) | 0 | 25 (12.4) | 25 (11.6) |
| Any serious TEAE, n(%) | 4 (25.0) | 1 (7.1) | 19 (9.4) | 20 (9.3) |
| TEAE leading to end of treatment, n (%) | 1 (6.3) | 0 | 3 (1.5) | 3 (1.4) |
Conclusions
The results indicate that niraparib tolerability will be improved with a starting dose based on body weight or platelet count.
Clinical trial identification
NCT03705156.
Editorial acknowledgement
Jun Wan and John Zhang of Zai Lab Writing and coordinated by Sean Li and Wendy Zhang of Zai Lab, Inc, funded by Zai Lab, Inc. (Shanghai,China).
Legal entity responsible for the study
Zai Lab (Shanghai) Co., Ltd.
Funding
Zai Lab (Shanghai) Co., Ltd.
Disclosure
J. Hou: Full / Part-time employment: Zai Lab (Shanghai) Co., Ltd C. Zhang: Full / Part-time employment: Zai Lab (Shanghai) Co., Ltd Y. Hei: Full / Part-time employment: Zai Lab (Shanghai) Co., Ltd. All other authors have declared no conflicts of interest.
Resources from the same session
5629 - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumor infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion
Presenter: Luca Campedel
Session: Poster Display session 2
Resources:
Abstract
5792 - A novel PET parameter for cancer stem cell metabolism: early prediction of chemosensitivity to neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Chanwoo Kim
Session: Poster Display session 2
Resources:
Abstract
3728 - Using nodal ratio to predict recurrence in patients with 4 or more positive lymph nodes early stage breast cancer
Presenter: Besma Graja
Session: Poster Display session 2
Resources:
Abstract
3395 - Re-sentinel node biopsy for local recurrence after breast-conserving surgery
Presenter: Yuka Matsubara
Session: Poster Display session 2
Resources:
Abstract
4302 - Assessment of prognostic and therapeutic factors in men with breast cancer
Presenter: Daniel Herrero Rivera
Session: Poster Display session 2
Resources:
Abstract
4263 - Genomic Profiling of Chinese Breast Cancer Patients
Presenter: Zhonghua Tao
Session: Poster Display session 2
Resources:
Abstract
2406 - Genome copy number alteration burden represents predictor of response in long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer
Presenter: Naomi Walsh
Session: Poster Display session 2
Resources:
Abstract
2575 - Next-generation DNA Sequencing (NGS) Results for Tumors From Phase 2 ABRAZO Study of Talazoparib After Platinum or Cytotoxic Non-Platinum Regimens in Patients (pts) With Advanced Breast Cancer (ABC) and Germline BRCA1/2 (gBRCA) Mutations
Presenter: Nicholas C. Turner
Session: Poster Display session 2
Resources:
Abstract
4499 - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors
Presenter: Evgeny Imyanitov
Session: Poster Display session 2
Resources:
Abstract
4110 - Clinicopathologic features of BRCA mutated breast cancer patients: Hacettepe Experience
Presenter: Sercan Aksoy
Session: Poster Display session 2
Resources:
Abstract