Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy : A Randomized, Double-Blind, Phase 3 Study
Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved..
INTRODUCTION: ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC).
METHODS: Patients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety.
RESULTS: ZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018-February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41-2.69, niraparib) and 1.36 months (1.31-1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46-0.95, p = 0.0242). Median overall survival was 9.92 months (9.33-13.54, niraparib) and 11.43 months (9.53-not estimable, placebo); HR = 1.03 (95% CI: 0.62-1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41-2.56, niraparib) and 1.41 months (1.31-2.00, placebo); HR = 0.88 (95% CI: 0.61-1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients.
CONCLUSIONS: ZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.
| Errataetall: |
CommentIn: J Thorac Oncol. 2021 Aug;16(8):1236-1238. - PMID 34304849 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
|---|---|
| Enthalten in: |
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer - 16(2021), 8 vom: 09. Aug., Seite 1403-1414 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ai, Xinghao [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 09.08.2021 Date Revised 09.08.2021 published: Print-Electronic CommentIn: J Thorac Oncol. 2021 Aug;16(8):1236-1238. - PMID 34304849 Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jtho.2021.04.001 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM324685041 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM324685041 | ||
| 003 | DE-627 | ||
| 005 | 20231225190837.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jtho.2021.04.001 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1082.xml |
| 035 | |a (DE-627)NLM324685041 | ||
| 035 | |a (NLM)33915252 | ||
| 035 | |a (PII)S1556-0864(21)02111-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ai, Xinghao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy |b A Randomized, Double-Blind, Phase 3 Study |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.08.2021 | ||
| 500 | |a Date Revised 09.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: J Thorac Oncol. 2021 Aug;16(8):1236-1238. - PMID 34304849 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a INTRODUCTION: ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC) | ||
| 520 | |a METHODS: Patients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety | ||
| 520 | |a RESULTS: ZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018-February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41-2.69, niraparib) and 1.36 months (1.31-1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46-0.95, p = 0.0242). Median overall survival was 9.92 months (9.33-13.54, niraparib) and 11.43 months (9.53-not estimable, placebo); HR = 1.03 (95% CI: 0.62-1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41-2.56, niraparib) and 1.41 months (1.31-2.00, placebo); HR = 0.88 (95% CI: 0.61-1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients | ||
| 520 | |a CONCLUSIONS: ZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Chinese | |
| 650 | 4 | |a Extensive-stage small cell lung cancer | |
| 650 | 4 | |a Maintenance | |
| 650 | 4 | |a Niraparib | |
| 650 | 4 | |a PARP inhibitor | |
| 650 | 7 | |a Indazoles |2 NLM | |
| 650 | 7 | |a Piperidines |2 NLM | |
| 650 | 7 | |a niraparib |2 NLM | |
| 650 | 7 | |a HMC2H89N35 |2 NLM | |
| 700 | 1 | |a Pan, Yueyin |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Nong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chunling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jianying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaodong |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Xiaorong |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jianxing |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiaoling |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Gongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xingya |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Helong |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Wangjun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yiping |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Zhiyong |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Liyan |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Jiuwei |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Chunhong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Cuimin |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xiaohua |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Beili |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaoqing |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Jianping |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Anwen |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Junling |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yinyin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Mengzhao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Biao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Shun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer |d 2006 |g 16(2021), 8 vom: 09. Aug., Seite 1403-1414 |w (DE-627)NLM169435504 |x 1556-1380 |7 nnns |
| 773 | 1 | 8 | |g volume:16 |g year:2021 |g number:8 |g day:09 |g month:08 |g pages:1403-1414 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jtho.2021.04.001 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 16 |j 2021 |e 8 |b 09 |c 08 |h 1403-1414 | ||