Intracranial Activity of Selpercatinib in Chinese Patients With Advanced<i>RET</i>Fusion–Positive Non–Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial-Reference-Cited by-同舟云学术

Intracranial Activity of Selpercatinib in Chinese Patients With AdvancedRETFusion–Positive Non–Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial

Published:2023-09 Issue:7 Volume: Page:
ISSN:2473-4284
Container-title:JCO Precision Oncology
language:en
Short-container-title:JCO Precision Oncology

Author:

Cheng Ying¹^ORCID,Huang Dingzhi²,Zhou Jianying³,Zhou Chengzhi⁴,Sun Yuping⁵,Wu Lin⁶^ORCID,Guo Ye⁷,Jingxin Shao⁸,Zhang Wanli⁸,Lu Shun⁹^ORCID

Affiliation:

1. Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China

2. Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

3. Department of Respiratory Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

4. Respiratory Medicine Department, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

5. Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, China

6. Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan, China

7. Department of Medical Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

8. Department of Oncology, Eli Lilly and Company, Shanghai, China

9. Department of Medical Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China

Abstract

PURPOSESelpercatinib, a highly selective, potent RET inhibitor with CNS activity, demonstrated sustained antitumor responses and intracranial activity in patients with RET-altered advanced non–small-cell lung cancer (NSCLC) in the global LIBRETTO-001 and Chinese LIBRETTO-321 trials. We report a prospective case series based on updated data from patients with brain metastases at baseline in LIBRETTO-321.MATERIALS AND METHODSWe included patients with advanced NSCLC and brain metastasis with a centrally confirmed KIF5B/ CCDC6/ NCOA4-RET fusion. Patients with previously treated or untreated CNS metastases were included if asymptomatic or neurologically stable. Patients received oral selpercatinib 160 mg, twice daily, until progression. Objective systemic and intracranial response was independently assessed per RECIST v1.1. The data cutoff (DCO) was March 31, 2022.RESULTSIn total, 8/26 (31%) patients were included: 1/8 (13%) had previous brain surgery but no previous systemic therapy and 3/8 (38%) had received brain radiotherapy. Best overall systemic response was partial response (PR) in 6/8 patients (75%) and stable disease (SD) in 2/8 (25%). Among patients with measurable baseline CNS lesions, 4/5 (80%) achieved a confirmed intracranial response (3/5 PRs and 1/5 complete response [CR]). The best overall intracranial response was CR in 3/8 (38%), PR in 3/8 (38%), and SD in 1/8 (13%) and nonprogressive disease/non-CR in 1/8 (13%); 2/8 patients (25%) had CNS-only disease progression. The duration of treatment was 2.8-24.0 months, and 5/8 patients (63%) had treatment ongoing at DCO. Of 8 patients, 5 (63%) had grade ≥3 treatment-related adverse events (TRAEs) requiring dose modification. There were no treatment discontinuations because of TRAEs.CONCLUSIONSelpercatinib demonstrated clinically meaningful and durable intracranial activity in Chinese patients with brain metastases from RET-altered NSCLC, consistent with the global LIBRETTO-001 trial.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

Link

https://ascopubs.org/doi/pdfdirect/10.1200/PO.22.00708

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1. Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001;Cancers;2023-12-27

2. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion–Positive NSCLC;New England Journal of Medicine;2023-11-16

3. Erratum: Intracranial Activity of Selpercatinib in Chinese Patients With Advanced RET Fusion–Positive Non–Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial;JCO Precision Oncology;2023-09