Selpercatinib在治疗RET融合阳性NSCLC患者中的应用：LIBRETTO-001一/二期注册试验最新安全性和有效性

SCI

11 October 2022

The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma

（IF: JCO, 50.717）

Drilon A, Subbiah V, Gautschi O, Tomasini P, de Braud F, Solomon BJ, Shao-Weng Tan D, Alonso G, Wolf J, Park K, Goto K, Soldatenkova V, Szymczak S, Barker SS, Puri T, Bence Lin A, Loong H, Besse B. Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. J Clin Oncol. 2022 Sep 19:JCO2200393. 

CORRESPONDING AUTHOR Alexander Drilon, MD, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY 10065; e-mail: drilona@mskcc.org.

PURPOSE 目的

Selpercatinib, a first-in-class, highly selective, and potent CNS-active RET kinase inhibitor, is currently approved for the treatment of patients with RET fusion–positive non–small-cell lung cancer (NSCLC).We provide a registrational data set up date in more than double (n=5316)of the original reported population (n=5144) and better characterization of long-term efficacy and safety. 

Selpercatinib是一种同类最优的创新药，是具有高选择性和强效的中枢神经系统活性RET激酶抑制剂，目前已被批准用于治疗RET融合阳性非小细胞肺癌（NSCLC）患者。我们提供的注册数据的设定日期是原始报告人群（n=5144）的两倍多（n=5316），并更好地描述了长期的有效性和安全性。

METHODS 方法

Patients were enrolled to LIBRETTO-001, a phaseI/II, single-arm, open-label study of selpercatinib in patients with RET-altered cancers. An analysis of patients with RET fusion–positive NSCLC, including 69 treatment-naive and 247 with prior platinum-based chemotherapy, was performed. The primary end point was objective response rate (ORR; RECIST v1.1, independent review committee). Secondary end points included duration of response (DoR), progression-free survival (PFS), overall survival, and safety. 

患者入组LIBRETTO-001，这是一项针对selpercatinib治疗RET改变的癌症患者的I/II期、单臂、开放标签研究。对RET融合阳性NSCLC患者进行了分析，包括69例初治患者和247例既往接受过铂类化疗的患者。主要终点是客观缓解率（ORR；RECIST v1.1，独立审查委员会）。次要终点包括缓解持续时间（DoR）、无进展生存期（PFS）、总生存期和安全性。

RESULTS 结果

Intreatment-naïve patients, the ORR was 84% (95% CI,73 to 92);6% achieved complete responses (CRs). The median DoR was 20.2 months (95% CI, 13.0 to could not be evaluated); 40% of responses were ongoing at the data cutoff (median follow-up of 20.3 months). The median PFS was 22.0 months; 35% of patients were alive and progression-free at the data cutoff (median follow-up of 21.9 months). In platinum based chemotherapy pretreated patients, the ORR was 61% (95% CI, 55 to 67); 7% achieved CRs. The median DoR was 28.6 months (95% CI, 20.4 to could not be evaluated); 49% of responses were ongoing (median follow-up of 21.2 months). The median PFS was 24.9 months; 38% of patients were alive and progression-free (median follow-up of 24.7 months). Of 26 patients with measurable baseline CNS metastasis by the independent review committee, the intracranial ORR was 85% (95% CI, 65 to 96); 27% were CRs. In the full safety population (n=5796), the median treatment duration was 36.1 months. The safety profile of selpercatinib was consistent with previous reports. 

在初治患者中，ORR为84%（95% CI，73-92）；6%的人达到了完全缓解（CR）。中位DoR为20.2个月（95% CI, 13.0-无法评估）；40%的缓解在数据截止时仍在进行（中位随访时间20.3个月）。中位PFS为22.0个月；35%的患者在数据截止时仍然存活且无进展（中位随访时间21.9个月）。在以铂类为基础的化疗预处理的患者中，ORR为61%（95% CI，55-67）；7% 达到CR。中位DoR为28.6个月（95% CI，20.4-无法评估）；49%的患者缓解正在进行中（中位随访时间21.2个月）。中位PFS为24.9个月；38%的患者存活且无进展（中位随访时间24.7个月）。在独立审查委员会评估的26例基线可测量的CNS转移患者中，颅内ORR为85%（95% CI，65-96）；27%为CR。在完全安全人群中（n=5796），中位治疗持续时间为36.1个月。selpercatinib的安全性与之前的报告一致。

Conclusion 结论

In a large cohort with extended follow-up, selpercatinib continued to demonstrate durable and robust responses, including intracranial activity, in previously treated and treatment-naive patients with RET fusion–positive NSCLC.

在一个长期随访的大型队列研究中，在RET融合阳性NSCLC患者中，selpercatinib继续表现出针对包括颅内活动在内的持久和稳健的缓解。