据印度代购了解，在2021年美国临床肿瘤学会（ASCO）年会上公布了正在进行的1/2期LIBRETTO-121试验（NCT03899792）的数据，该数据显示塞尔帕替尼（selpercatinib,Retevmo）对患有RET改变型实体瘤的儿童患者具有抗肿瘤活性。在8例疾病可测量的患者中，客观缓解率（ORR）为50%（95%CI,16%-84%）。4例达到部分缓解（PR），2例疾病稳定（SD），1例疾病进展（PD），1例无法评估，临床受益率为75%（95%CI,35%-97%）。RET融合是乳头状甲状腺癌（PTC）患儿中最常见的可操作改变，大多数甲状腺髓样癌（MTC）患儿的生殖系RET突变与MEN2综合征有关。

Data from the ongoing Phase 1/2 LIBRETTO 121 trial (NCT03899792) were presented at the 2021 Annual Meeting of the American Society of Clinical Oncology (ASCO), These data demonstrate the antitumor activity of selpercatinib (Retevmo) in pediatric patients with RET - altered solid tumors. In eight patients with measurable disease, the objective response rate (ORR) was 50% (95%CI,16%-84%). Partial response (PR) was achieved in 4 patients, disease stability (SD) was achieved in 2 patients, disease progression (PD) was achieved in 1 patient, and the clinical benefit rate was 75% (95%CI,35%-97%). RET fusion is the most common operable change in children with papillary thyroid cancer (PTC), and most of the germline RET mutations in children with medullary thyroid cancer (MTC) are associated with MEN2 syndrome.

　　据印度代购了解，塞尔帕替尼是一种具有中枢神经系统（CNS）活性的高选择性和强效RET抑制剂，被批准用于治疗转移性RET融合阳性非小细胞肺癌成年患者、晚期或转移性RET突变型MTC成年和12岁及以上儿童患者（需要系统治疗）、晚期或转移性RET融合阳性甲状腺癌成年和12岁及以上儿童患者（需要系统治疗，并且放射性碘难治）。该药在成年患者中的良好疗效和安全性为其在儿科人群中的评估奠定了基础。

　　据印度代购了解，截至2021年3月30日（数据截止日期），共招募了12名患者。患者的中位年龄为14岁（范围2-20岁），男性6例，女性6例。大多数患者为MTC（n=8），其次为PTC（n=2）、横纹肌肉瘤（n=1）和骨肉瘤（n=1）。两例肉瘤患者的RET中都存在未知变异。缓解数据显示这1例骨肉瘤患者出现PD,而其他所有甲状腺癌和RET畸变患者出现SD或PR.另外的结果显示，首次服用塞尔帕替尼后，中位随访8个月，中位无进展生存期未达到。从最初的缓解开始，中位随访5个月，中位缓解持续时间未达到，所有4个PR都在进行中。重要的是，该试验招募的患者中，绝大多数（12人中的9人）仍在接受治疗。

　　据印度代购了解，值得注意的是，所有8例MTC患者无论其放射学反应如何，都经历了生物化学应答——降钙素减少和癌胚抗原可变减少。关于安全性，服用起始剂量的塞尔帕替尼时，没有报告剂量限制性毒性，该剂量被确定为2期推荐剂量。在扩展队列中，1名患者因PD而停止治疗，1名患者因不依从而停止治疗，1名患者因治疗无关不良反应（AE）而停止治疗。总的来说，该药耐受性很好，毒性很小，与在成年人中用药的经验一致。最常见的不良反应是腹泻、高磷血症、恶心和肝酶异常。尽管儿童患者的数据相当稀少，但重要的是，该药在儿童群体中的表现与在成年人中类似，支持在扩展队列中继续使用该剂量。

It is noteworthy that all eight MTC patients, regardless of their radiological response, experienced a biochemical response - a reduction in calcitonin and a variable reduction in carcinoembryonic antigen, according to Indian Dealmaking. With regard to safety, no dose-limiting toxicity was reported with the initial dose of serpatinib, which was identified as the Phase 2 recommendation. In the extended cohort, 1 patient stopped treatment due to PD, 1 patient stopped treatment due to noncompliance, and 1 patient stopped treatment due to treatment-unrelated adverse effects (AE). Overall, the drug was well tolerated with minimal toxicity, consistent with experience with administration in adults. The most common adverse reactions were diarrhea, hyperphosphatemia, nausea, and abnormal liver enzymes. Although data on pediatric patients are fairly sparse, it is important to note that the performance of the drug in children is similar to that in adults, supporting the continued use of the dose in the extended cohort.