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.
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.
复制标题
DOI：
10.1200/jco.22.00393
复制
发表时间：
2023-01-10
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
Selpercatinib是一种一流的、高选择性和强效的CNS活性RET激酶抑制剂，目前已获批用于治疗RET融合阳性非小细胞肺癌（NSCLC）患者。我们提供了超过原始报告人群（n = 144）两倍（n = 316）的登记数据集更新，并更好地表征了长期疗效和安全性。患者入组LIBRETTO-001，这是一项在RET改变的癌症患者中进行的selpercatinib 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。主要终点为客观缓解率（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。在初治患者中，ORR为84%（95% CI，73 - 92）; 6%达到完全缓解（CR）。中位DoR为20.2个月（95% CI，13.0至无法评价）; 40%的缓解在数据截止时仍在进行中（中位随访时间为20.3个月）。中位PFS为22.0个月; 35%的患者在数据截止时存活且无进展（中位随访时间为21.9个月）。在铂类化疗预治疗患者中，ORR为61%（95% CI，55 - 67）; 7%达到CR。中位DoR为28.6个月（95% CI，20.4至无法评估）; 49%的缓解正在进行中（中位随访时间为21.2个月）。中位PFS为24.9个月; 38%的患者存活且无进展（中位随访时间为24.7个月）。在独立审查委员会评估的基线CNS转移可测量的26例患者中，颅内ORR为85%（95% CI，65 - 96）; 27%为CR。在全安全性人群（n = 796）中，中位治疗持续时间为36.1个月。selpercatinib的安全性特征与既往报告一致。在一个具有延长随访的大型队列中，selpercatinib在既往接受过治疗和未经治疗的RET融合阳性NSCLC患者中继续表现出持久和稳健的缓解，包括颅内活性。
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 update in more than double (n = 316) of the original reported population (n = 144) and better characterization of long-term efficacy and safety. Patients were enrolled to LIBRETTO-001, a phase I/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. In treatment-naive 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 = 796), the median treatment duration was 36.1 months. The safety profile of selpercatinib was consistent with previous reports. 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.