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

被引：41

作者：

Ai, Xinghao ^{[1
]}

Pan, Yueyin ^{[2
]}

Shi, Jianhua ^{[3
]}

Yang, Nong ^{[4
]}

Liu, Chunling ^{[5
]}

Zhou, Jianying ^{[6
]}

Zhang, Xiaodong ^{[7
]}

Dong, Xiaorong ^{[8
]}

He, Jianxing ^{[9
]}

Li, Xiaoling ^{[10
]}

Chen, Gongyan ^{[11
]}

Li, Xingya ^{[12
]}

Zhang, Helong ^{[13
]}

Liao, Wangjun ^{[14
]}

Zhang, Yiping ^{[15
]}

Ma, Zhiyong ^{[16
]}

Jiang, Liyan ^{[17
]}

Cui, Jiuwei ^{[18
]}

Hu, Chunhong ^{[19
]}

Wang, Wei ^{[20
]}

Huang, Cheng ^{[21
]}

Zhao, Jun ^{[22
]}

Ding, Cuimin ^{[23
,24
]}

Hu, Xiaohua ^{[25
]}

Wang, Kai ^{[26
]}

Gao, Beili ^{[27
]}

Song, Yong ^{[28
]}

Liu, Xiaoqing ^{[29
]}

Xiong, Jianping ^{[30
]}

Liu, Anwen ^{[31
]}

Li, Junling ^{[32
]}

Liu, Zhe ^{[33
]}

Li, Yinyin ^{[34
]}

Wang, Mengzhao ^{[35
]}

Zhang, Biao ^{[36
]}

Zhang, Dan ^{[36
]}

Lu, Shun ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai Lung Canc Ctr, 241 West Huaihai Rd, Shanghai 200030, Peoples R China

[2] Anhui Prov Hosp, Dept Chemotherapy, Hefei, Peoples R China

[3] Linyi Canc Hosp, Dept Med Oncol, Linyi, Shandong, Peoples R China

[4] Hunan Canc Hosp, Lung & Gastrointestinal Oncol Dept, Changsha, Peoples R China

[5] Xinjiang Med Univ, Dept Pulm Med, Canc Hosp, Urumqi, Peoples R China

[6] Zhejiang Univ, Affiliated Hosp 1, Dept Resp Med, Hangzhou, Peoples R China

[7] Nantong Tumor Hosp, Dept Med Oncol, Nantong, Peoples R China

[8] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Canc Ctr, Wuhan, Peoples R China

[9] Guangzhou Med Univ, Dept Thorac Surg, Affiliated Hosp 1, Guangzhou, Peoples R China

[10] Liaoning Canc Hosp & Inst, Dept Thorac Med, Shenyang, Peoples R China

[11] Harbin Med Univ, Dept Resp Med, Canc Hosp, Harbin, Peoples R China

[12] Zhengzhou Univ, Dept Oncol, Affiliated Hosp 1, Zhengzhou, Peoples R China

[13] Tangdu Hosp, Dept Oncol, Xian, Peoples R China

[14] Nanfang Hosp, Dept Oncol, Guangzhou, Peoples R China

[15] Zhejiang Canc Hosp, Dept Thorac Med Oncol, Hangzhou, Peoples R China

[16] Zhengzhou Univ, Dept Resp Med, Affiliated Canc Hosp, Henan Canc Hosp, Zhengzhou, Peoples R China

[17] Shanghai Chest Hosp, Dept Resp, Shanghai, Peoples R China

[18] Jilin Univ, Dept Oncol, Bethune Hosp 1, Changchun, Peoples R China

[19] Cent South Univ, Dept Oncol, Xiangya Hosp 2, Changsha, Peoples R China

[20] Jinzhou Cent Hosp, Dept Oncol, Jinzhou, Peoples R China

[21] Fujian Canc Hosp, Dept Oncol, Fuzhou, Peoples R China

[22] Peking Univ, Dept Thorac Oncol, Canc Hosp & Inst, Beijing, Peoples R China

[23] Hebei Med Univ, Dept Resp Med, Hosp 4, Shijiazhuang, Hebei, Peoples R China

[24] Hebei Canc Hosp, Shijiazhuang, Hebei, Peoples R China

[25] Guangxi Med Univ, Dept Oncol, Affiliated Hosp 1, Nanning, Peoples R China

[26] Zhejiang Univ, Dept Resp Med, Affiliated Hosp 2, Sch Med, Hangzhou, Peoples R China

[27] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Resp Med, Sch Med, Shanghai, Peoples R China

[28] Nanjing Mil Command, Dept Resp Med, Nanjing Gen Hosp, Nanjing, Peoples R China

[29] 307th Hosp Chinese Peoples Liberat Army, Dept Pulm Oncol, Beijing, Peoples R China

[30] Nanchang Univ, Dept Oncol, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China

[31] Nanchang Univ, Dept Oncol, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China

[32] Chinese Acad Med Sci, Dept Internal Med, Canc Hosp, Beijing, Peoples R China

[33] Capital Med Univ, Beijing Chest Hosp, Dept Oncol, Beijing, Peoples R China

[34] Shenyang Tenth Peoples Hosp, Dept Oncol, Shenyang, Peoples R China

[35] Peking Union Med Coll Hosp, Dept Resp Med, Beijing, Peoples R China

[36] Zai Lab Shanghai Co Ltd, R&D Dept, Shanghai, Peoples R China

来源：

JOURNAL OF THORACIC ONCOLOGY | 2021年 / 16卷 / 08期

关键词：

PARP inhibitor; Niraparib; Extensive-stage small cell lung cancer; Maintenance; Chinese; CELL LUNG-CANCER; OVARIAN-CANCER; THERAPY; PLUS;

D O I：

10.1016/j.jtho.2021.04.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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/mL] 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. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

引用

页码：1403 / 1414

页数：12

共 30 条

[1] Treatment for small cell lung cancer, where are we now?-a review
Alvarado-Luna, Gabriela
Morales-Espinosa, Daniela
[J]. TRANSLATIONAL LUNG CANCER RESEARCH, 2016, 5 (01) : 26 - 38
[2] Safety and dose modification for patients receiving niraparib
Berek, J. S.
Matulonis, U. A.
Peen, U.
Ghatage, P.
Mahner, S.
Redondo, A.
Lesoin, A.
Colombo, N.
Vergote, I.
Rosengarten, O.
Ledermann, J.
Pineda, M.
Ellard, S.
Sehouli, J.
Gonzalez-Martin, A.
Berton-Rigaud, D.
Madry, R.
Reinthaller, A.
Hazard, S.
Guo, W.
Mirza, M. R.
[J]. ANNALS OF ONCOLOGY, 2018, 29 (08) : 1784 - 1792
[3] Small Cell Lung Cancer: Where Do We Go From Here?
Byers, Lauren Averett
Rudin, Charles M.
[J]. CANCER, 2015, 121 (05) : 664 - 672
[4] Proteomic Profiling Identifies Dysregulated Pathways in Small Cell Lung Cancer and Novel Therapeutic Targets Including PARP1
Byers, Lauren Averett
Wang, Jing
Nilsson, Monique B.
Fujimoto, Junya
Saintigny, Pierre
Yordy, John
Giri, Uma
Peyton, Michael
Fan, You Hong
Diao, Lixia
Masrorpour, Fatemeh
Shen, Li
Liu, Wenbin
Duchemann, Boris
Tumula, Praveen
Bhardwaj, Vikas
Welsh, James
Weber, Stephanie
Glisson, Bonnie S.
Kalhor, Neda
Wistuba, Ignacio I.
Girard, Luc
Lippman, Scott M.
Mills, Gordon B.
Coombes, Kevin R.
Weinstein, John N.
Minna, John D.
Heymach, John V.
[J]. CANCER DISCOVERY, 2012, 2 (09) : 798 - 811
[5] The role of Schlafen 11 (SLFN11) as a predictive biomarker for targeting the DNA damage response
Coleman, Niamh
Zhang, Bingnan
Byers, Lauren A.
Yap, Timothy A.
[J]. BRITISH JOURNAL OF CANCER, 2021, 124 (05) : 857 - 859
[6] Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial
Coleman, Robert L.
Oza, Amit M.
Lorusso, Domenico
Aghajanian, Carol
Oaknin, Ana
Dean, Andrew
Colombo, Nicoletta
Weberpals, Johanne, I
Clamp, Andrew
Scambia, Giovanni
Leary, Alexandra
Holloway, Robert W.
Amenedo Gancedo, Margarita
Fong, Peter C.
Goh, Jeffrey C.
O'Malley, David M.
Armstrong, Deborah K.
Garcia-Donas, Jesus
Swisher, Elizabeth M.
Floquet, Anne
Konecny, Gottfried E.
McNeish, lain A.
Scott, Clare L.
Cameron, Terri
Maloney, Lara
Isaacson, Jeff
Goble, Sandra
Grace, Caroline
Harding, Thomas C.
Raponi, Mitch
Sun, James
Lin, Kevin K.
Giordano, Heidi
Ledermann, Jonathan A.
[J]. LANCET, 2017, 390 (10106) : 1949 - 1961
[7] Adding PD-1/PD-L1 Inhibitors to Chemotherapy for the First-Line Treatment of Extensive Stage Small Cell Lung Cancer (SCLC): A Meta-Analysis of Randomized Trials
Facchinetti, Francesco
Di Maio, Massimo
Tiseo, Marcello
[J]. CANCERS, 2020, 12 (09) : 1 - 18
[8] Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses in BRCA Carrier Ovarian Cancer Correlating With Platinum-Free Interval
Fong, Peter C.
Yap, Timothy A.
Boss, David S.
Carden, Craig P.
Mergui-Roelvink, Marja
Gourley, Charlie
De Greve, Jacques
Lubinski, Jan
Shanley, Susan
Messiou, Christina
A'Hern, Roger
Tutt, Andrew
Ashworth, Alan
Stone, John
Carmichael, James
Schellens, Jan H. M.
de Bono, Johann S.
Kaye, Stan B.
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (15) : 2512 - 2519
[9] Targeted Therapy and Immune Therapy for Small Cell Lung Cancer
Gadgeel, Shirish M.
[J]. CURRENT TREATMENT OPTIONS IN ONCOLOGY, 2018, 19 (11)
[10] Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities
Gay, Carl M.
Stewart, C. Allison
Park, Elizabeth M.
Diao, Lixia
Groves, Sarah M.
Heeke, Simon
Nabet, Barzin Y.
Fujimoto, Junya
Solis, Luisa M.
Lu, Wei
Xi, Yuanxin
Cardnell, Robert J.
Wang, Qi
Fabbri, Giulia
Cargill, Kasey R.
Vokes, Natalie, I
Ramkumar, Kavya
Zhang, Bingnan
Della Corte, Carminia M.
Robson, Paul
Swisher, Stephen G.
Roth, Jack A.
Glisson, Bonnie S.
Shames, David S.
Wistuba, Ignacio I.
Wang, Jing
Quaranta, Vito
Minna, John
Heymach, John, V
Byers, Lauren Averett
[J]. CANCER CELL, 2021, 39 (03) : 346 - +

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