Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan
Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan
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DOI：
10.1158/1078-0432.ccr-17-0933
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发表时间：
2017-10-01
影响因子：
11.5
通讯作者：
Goldenberg, David M.
中科院分区：
文献类型：
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作者：
Gray, Jhanelle E.;Heist, Rebecca S.;Goldenberg, David M.
目的：我们评估了一种靶向trop -2的抗体结合SN-38在转移性小细胞肺癌（mSCLC）患者中的作用。实验设计：研究了Sacituzumab govitecan在21天周期的第1天和第8天接受8或10 mg/kg静脉注射的预处理（中位数，2；范围，1-7）mSCLC患者中的应用。主要终点为安全性和客观缓解率（ORR）；缓解时间、无进展生存期（PFS）和总生存期（OS）是次要终点。结果：60%的患者在基线ct上显示肿瘤缩小。在意向治疗基础上（N = 50）， ORR为14% (10 mg/kg组为17%)；中位缓解持续时间为5.7个月；临床获益率（CBR >= 4个月），34%；中位PFS， 3.7个月；中位OS为7.5个月。在对一线治疗敏感的二线患者中，使用sacituzumab govitecan可改善PR、CBR和PFS，但在总体人群中，一线化疗敏感患者与化疗耐药患者之间没有差异。在一个小的亚组中，先前接受拓扑替康治疗的患者与未接受拓扑替康治疗的患者相比，有统计学意义的更高的OS。>= 3级不良事件包括中性粒细胞减少（34%）、疲劳（13%）、腹泻（9%）和贫血（6%）。患者选择不需要Trop-2肿瘤染色。在连续的血液采集中未检测到该药物偶联物或其成分的抗体。结论：Sacituzumab govitecan似乎对重度预处理的mSCLC患者具有安全有效的治疗效果，包括那些对一线化疗化疗敏感或耐药的患者。作为单一疗法或联合疗法的进一步研究是必要的。(c) 2017 aacr。
Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR >= 4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade >= 3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. (C) 2017 AACR.