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
3907 - Exploration of efficacious alternative regorafenib regimens to manage hand-foot-skin-reaction (HFSR)
Presenter: Axel Grothey
Session: Poster Display session 2
Resources:
Abstract
3958 - Quality of Life (QoL) in Metastatic Colorectal Cancer (mCRC) in the Real World: Final Results of a European Survey
Presenter: Zorana Maravic
Session: Poster Display session 2
Resources:
Abstract
3563 - BISQUIT: A Randomized Phase II Study of the Administration of Prebiotics and Probiotics During Definitive Treatment With Chemotherapy-radiotherapy for Patients With Squamous Cell Carcinoma of the Anal Canal
Presenter: Rachel Riechelmann
Session: Poster Display session 2
Resources:
Abstract
1184 - iSCORE: Immunotherapy Sequencing in COlon and REctal Cancer
Presenter: Fiona Turkes
Session: Poster Display session 2
Resources:
Abstract
3346 - Phase II study of preoperative (PREOP) chemoradiotherapy (CTRT) plus avelumab (AVE) in patients (PTS) with locally advanced rectal cancer (LARC): The AVANA Study
Presenter: Lisa Salvatore
Session: Poster Display session 2
Resources:
Abstract
3895 - A phase II study of capecitabine plus concomitant radiation therapy followed by durvalumab (MEDI4736) as preoperative treatment in rectal cancer: PANDORA study.
Presenter: Maria Aurelia Barbera
Session: Poster Display session 2
Resources:
Abstract
2012 - Open Label Phase III Study of Arfolitixorin vs. Leucovorin in mFOLFOX-6 for First Line Treatment of Metastatic Colorectal Cancer: AGENT
Presenter: Josep Tabernero
Session: Poster Display session 2
Resources:
Abstract
2198 - SOLSTICE, a phase 3, randomized, open label study of trifluridine/tipiracil+bevacizumab (bev) versus capecitabine+bev for the 1L treatment of patients with unresectable metastatic colorectal cancer (mCRC) who are not candidates for intensive therapy
Presenter: Thierry Andre
Session: Poster Display session 2
Resources:
Abstract
2921 - A Phase Ib/ II Trial to Assess the Safety and Efficacy of CXD101 in Combination with the PD-1 Inhibitor Nivolumab in Patients with Metastatic, Previously-Treated, Microsatellite-Stable (MSS) Colorectal Carcinoma (short title CAROSELL)
Presenter: Mark Saunders
Session: Poster Display session 2
Resources:
Abstract
3695 - A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation
Presenter: Heinz Josef Lenz
Session: Poster Display session 2
Resources:
Abstract