干旱区生态环境知识资源中心(Arid): Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study

Arid

DOI	10.1016/j.jtho.2019.04.026
	Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study
	Thomas, Anish 1; Vilimas, Rasa 1; Trindade, Christopher 2; Erwin-Cohen, Rebecca 3; Roper, Nitin 4; Xi, Liqiang 2; Krishnasamy, Venkatesh 5; Levy, Elliot 5; Mammen, Andy 6; Nichols, Samantha 1; Chen, Yuanbin 7; Velcheti, Vamsidhar 8; Yin, Faye 9; Szabo, Eva 10; Pommier, Yves 1; Steinberg, Seth M.11; Trepel, Jane B.1; Raffeld, Mark 2; Young, Howard A.3; Khan, Javed 12; Hewitt, Stephen 2; Lee, Jung-Min 13
通讯作者	Thomas, Anish
来源期刊	JOURNAL OF THORACIC ONCOLOGY
ISSN	1556-0864
EISSN	1556-1380
出版年	2019
卷号	14 期号:8 页码:1447-1457
英文摘要	Purpose: Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. Methods: A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells in direct contact with tumor). Results: A total of 20 patients were enrolled. Their median age was 64 years, and most patients (60%) had platinum-resistant/refractory disease. Of 19 evaluable patients, two were observed to have partial or complete responses (10.5%), including a patient with EGFR-transformed SCLC. Clinical benefit was observed in four patients (21.1% [95% confidence interval: 6.1%-45.6%]) with confirmed responses or prolonged stable disease (>= 8 months). The most common treatment-related adverse events were anemia (80%), lymphopenia (60%), and leukopenia (50%). Nine of 14 tumors (64%) exhibited an excluded phenotype; 21% and 14% of tumors exhibited the inflamed and desert phenotypes, respectively. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Of the five tumors without an inflamed phenotype at baseline, no during-treatment increase in Tcell infiltration or programmed death ligand 1 expression on tumor-infiltrating immune cells was observed. Conclusions: The study combination did not meet the preset bar for efficacy. Pretreatment and during-treatment biopsy specimens suggested that tumor immune phenotypes may be relevant for SCLC responses to immune checkpoint blockade combinations. The predictive value of preexisting CD8-positive T-cell infiltrates observed in this study needs to be confirmed in larger cohorts. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.
英文关键词	Small cell lung cancer PARP inhibitors immune checkpoint blockade tumor immune phenotype DNA repair
类型	Article
语种	英语
国家	USA
开放获取类型	Green Accepted, Bronze
收录类别	SCI-E
WOS记录号	WOS:000476595900028
WOS关键词	CELL LUNG-CANCER ; PD-L1 EXPRESSION ; DOSE-ESCALATION ; OPEN-LABEL ; EXCLUSION ; BLOCKADE ; PARP1
WOS类目	Oncology ; Respiratory System
WOS研究方向	Oncology ; Respiratory System
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/217396
作者单位	1.NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA; 2.NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA; 3.NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA; 4.NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA; 5.NIH, Intervent Radiol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA; 6.NIAMSD, Muscle Dis Unit, Bethesda, MD 20892 USA; 7.Canc & Hematol Ctr Western Michigan, Grand Rapids, MI USA; 8.NYU, Thorac Med Oncol, Perlmutter Canc Ctr, New York, NY USA; 9.Western Maryland Reg Med Ctr, Schwab Family Canc Ctr, Cumberland, MD USA; 10.NCI, Canc Prevent Div, Bethesda, MD 20892 USA; 11.NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA; 12.NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA; 13.NCI, Womens Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA
推荐引用方式 GB/T 7714	Thomas, Anish,Vilimas, Rasa,Trindade, Christopher,et al. Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study[J],2019,14(8):1447-1457.
APA	Thomas, Anish.,Vilimas, Rasa.,Trindade, Christopher.,Erwin-Cohen, Rebecca.,Roper, Nitin.,...&Lee, Jung-Min.(2019).Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study.JOURNAL OF THORACIC ONCOLOGY,14(8),1447-1457.
MLA	Thomas, Anish,et al."Durvalumab in Combination with Olaparib in Patients with Relapsed SCLC: Results from a Phase II Study".JOURNAL OF THORACIC ONCOLOGY 14.8(2019):1447-1457.