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
3875 - Correlation of radiotherapy with the prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping
Presenter: Jin Zhang
Session: Poster Display session 2
Resources:
Abstract
5793 - Real world treatment sequencing patterns in secondary breast cancer (SBC): Pathway visualisation using national datasets.
Presenter: Ashley Horne
Session: Poster Display session 2
Resources:
Abstract
3185 - Utilization Pattern of Bone Targeting Agents in Patients with Solid Tumor in Taiwan, Hong Kong and Korea
Presenter: Shi Jie Lai
Session: Poster Display session 2
Resources:
Abstract
3705 - Clinico-pathological Features and Prognosis of Patients with Pregnancy Associated Breast Cancer – A Matched Case Control Study
Presenter: Ruyan Zhang
Session: Poster Display session 2
Resources:
Abstract
1421 - TRYbeCA-2: A Randomized Phase 2/3 Study of Eryaspase in Combination with Gemcitabine and Carboplatin Chemotherapy versus Chemotherapy Alone As First-Line Treatment in Patients with Metastatic or Locally Recurrent Triple-Negative Breast Cancer
Presenter: Ahmad Awada
Session: Poster Display session 2
Resources:
Abstract
4119 - CONTESSA TRIO: A Multinational, Multicenter, Phase 2 Study of Tesetaxel plus 3 Different PD-(L)1 Inhibitors in Patients with Metastatic Triple-Negative Breast Cancer (TNBC) and Tesetaxel Monotherapy in Elderly Patients with HER2- Metastatic Breast Cancer (MBC)
Presenter: Sara Tolaney
Session: Poster Display session 2
Resources:
Abstract
4545 - Bintrafusp alfa (M7824) and Eribulin Mesylate in Treating Patients With Metastatic Triple Negative Breast Cancer (TNBC)(NCT03579472)
Presenter: Jennifer Litton
Session: Poster Display session 2
Resources:
Abstract
3340 - Effectiveness of Olaparib Plus Trastuzumab in HER2[+], BRCA–mutated (BRCAm) or Homologous Recombination Deficient (HRD) Advanced Breast Cancer (ABC) patients (pts). The OPHELIA Study
Presenter: José Enrique Alés-Martínez
Session: Poster Display session 2
Resources:
Abstract
1113 - RIBOB : A Study on the efficacy and safety of Ribociclib in combination with letrozole in Older women (≥70 years) with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced Breast cancer (aBC) with no prior systemic therapy for advanced disease
Presenter: Cindy Kenis
Session: Poster Display session 2
Resources:
Abstract
4025 - RIbociclib plus Goserelin with Hormonal Therapy versus physician Choice chemotherapy in premenopausal or perimenopausal patients with HR+, HER2– inoperable locally advanced or metastatic breast cancer – RIGHT Choice study
Presenter: Nagi El Saghir
Session: Poster Display session 2
Resources:
Abstract