Trls-12. Efficacy and Safety of Entrectinib in Children Withntrk Orros1 Fusion-positive (fp) Primary Central Nervous System (cns) Tumors
Year: 2024
Type: conference-abstract
Abstract: BACKGROUND Entrectinib (CNS-penetrant, TRK/ROS1 inhibitor) has shown efficacy and safety in children with NTRK/ROS1-fp CNS tumors. We present updated data from an integrated analysis of children with NTRK/ROS1-fp CNS tumors enrolled in three early-phase trials: STARTRK-NG (NCT02650401), TAPISTRY (NCT04589845) and STARTRK-2 (NCT02568267). METHODS TRK/ROS1 inhibitor-naïve patients <18 years old (YO) with NTRK/ROS1-fp CNS tumors with measurable/evaluable-only disease, who received ≥1 entrectinib dose before disease progression, unacceptable toxicity, or consent withdrawal, and with ≥6 months’ follow-up were efficacy evaluable. Any <18 YO on study who received ≥1 entrectinib dose, regardless of genetic alteration and follow-up duration, was evaluable for safety. Primary endpoint: blinded independent central review (BICR)-assessed confirmed objective response rate (ORR). Key secondary endpoints: BICR-assessed confirmed ORR in patients with measurable disease; duration of confirmed response (DoR); time to confirmed response (TtR); progression-free survival (PFS); safety. RESULTS On 16 July 2023 (cut-off for analysis), 27 patients were efficacy evaluable (NTRK-fp: n=20; ROS1-fp: n=7). Median age at enrolment: 4.0 Y (NTRK-fp) and 6.0 Y (ROS1-fp); 45.0% (NTRK-fp) and 42.9% (ROS1-fp) of patients received ≥2 prior therapy lines. Median survival follow-up: 26.2 months (NTRK-fp); 36.1 months (ROS1-fp). ORR: 50.0% (NTRK-fp) and 71.4% (ROS1-fp) in efficacy-evaluable patients, and 58.8% (n=10/17; NTRK-fp) and 83.3% (n=5/6; ROS1-fp) in patients with measurable disease. Median DoR: 25.4 months, TtR: 1.9 months, PFS: 23.1 months in NTRK-fp patients. DoR and PFS were not evaluable in ROS1-fp patients; median TtR was 1.9 months. In the safety-evaluable population (N=34), the most common adverse events were weight increase (50.0%), blood creatinine increase and anemia (each 41.2%). Bone fractures were reported in 26.5% of patients. Most fractures occurred in children 2–12 YO (n=7/9). CONCLUSIONS Our analysis confirms the rapid and durable activity of entrectinib in children with NTRK/ROS1-fp primary CNS tumors. The safety profile described was in line with previous reports.
Source: Neuro-Oncology
Authors: Aditi Bagchi, Giles W Robinson, Ami V Desai, Yeming Wu, Huanmin Wang, Ellen M Basu, Michela Casanova, Cornelis M van Tilburg, Quentin Campbell-Hewson, Amy E Armstrong, Nicolas André, Clare Devlin, Jade Wulff, Alison Cardenas, Katherine E Hutchinson, Qinshu Lian, Carolina Ryklansky, Vesna Sneller Harmach, Elizabeth Fox, Amar Gajjar
Institutions: St. Jude Children's Research Hospital, University of Chicago Medical Center, Shanghai Jiao Tong University, XinHua Hospital, Capital Medical University, Beijing Children’s Hospital, Memorial Sloan Kettering Cancer Center, Casa Sollievo della Sofferenza, Fondazione IRCCS Istituto Nazionale dei Tumori, German Cancer Research Center, University Hospital Heidelberg, Hopp Children's Cancer Center Heidelberg, Newcastle upon Tyne Hospitals NHS Foundation Trust, Great North Children's Hospital, Washington University in St. Louis, Inserm, Aix-Marseille Université, Centre de Recherche en Cancérologie de Marseille, Roche (United Kingdom), Genentech, Roche (Switzerland)
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,389
OpenAlex ID: W4399787391