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@ARTICLE{Desai:299823,
author = {A. V. Desai and A. Bagchi and A. E. Armstrong and C. M. van
Tilburg$^*$ and E. M. Basu and G. W. Robinson and H. Wang
and M. Casanova and N. André and Q. Campbell-Hewson and Y.
Wu and A. Cardenas and B. Ci and C. Ryklansky and C. E.
Devlin and G. Meneses-Lorente and J. Wulff and K. E.
Hutchinson and A. Gajjar and E. Fox},
title = {{E}fficacy and safety of entrectinib in children with
extracranial solid or central nervous system ({CNS}) tumours
harbouring {NTRK} or {ROS}1 fusions.},
journal = {European journal of cancer},
volume = {220},
issn = {0959-8049},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2025-00560},
pages = {115308},
year = {2025},
abstract = {Entrectinib, a central nervous system (CNS)-penetrant
TRK/ROS1 inhibitor, has demonstrated clinical activity in
children with NTRK1/2/3 or ROS1 fusion-positive extracranial
solid and CNS tumours. We present integrated data of
entrectinib in children with NTRK or ROS1 fusion-positive
tumours from the STARTRK-NG, TAPISTRY, and STARTRK-2
trials.Efficacy analyses were undertaken on TRK/ROS1
inhibitor-naïve patients aged <18 years with
metastatic/locally advanced NTRK1/2/3 or ROS1
fusion-positive extracranial solid or CNS tumours who
received ≥1 entrectinib dose and had ≥6 months of
follow-up from enrolment. Tumour responses were confirmed by
blinded independent central review (BICR) per RECIST
v1.1/RANO criteria.BICR-assessed confirmed objective
response rate (cORR). Key secondary endpoints: duration of
response (DoR); time to response (TtR); safety.As of 16 July
2023, out of 91 safety-evaluable patients, 64 (NTRK: n=44;
ROS1: n=20) were efficacy evaluable. In the NTRK and ROS1
subgroups, respectively, median age was 4.0 years and 7.5
years; median survival follow-up was 24.2 months and 27.6
months. cORR was 72.7 $\%$ (NTRK, 95 $\%$ confidence
interval [CI]: 57.2-85.0) and 65.0 $\%$ (ROS1, 95 $\%$ CI:
40.8-84.6). Median DoR was not reached (NTRK, 95 $\%$ CI:
25.4-not evaluable [NE]); ROS1, 95 $\%$ CI: 16.2-NE); median
TtR was 1.9 months in both subgroups. The most frequently
reported treatment-related adverse events included weight
gain (35.2 $\%)$ and anaemia (31.9 $\%).Integrated$ data
from three trials confirm entrectinib induces rapid and
durable responses in children with NTRK or ROS1
fusion-positive tumours. The increased duration of safety
monitoring does not demonstrate new or cumulative toxicity.
Registered clinical trials: STARTRK-NG: NCT02650401;
TAPISTRY: NCT04589845; STARTRK-2: NCT02568267.},
keywords = {CNS tumours (Other) / Entrectinib (Other) / NTRK fusions
(Other) / Paediatric tumours (Other) / ROS1 fusions (Other)
/ ROS1 inhibitor (Other) / STARTRK-2 (Other) / STARTRK-NG
(Other) / TAPISTRY (Other) / TRK inhibitor (Other)},
cin = {B310 / HD01},
ddc = {610},
cid = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40086048},
doi = {10.1016/j.ejca.2025.115308},
url = {https://inrepo02.dkfz.de/record/299823},
}