Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
16
12
2021
accepted:
05
07
2022
pubmed:
13
8
2022
medline:
23
8
2022
entrez:
12
8
2022
Statut:
ppublish
Résumé
Oncogenic RET fusions occur in diverse cancers. Pralsetinib is a potent, selective inhibitor of RET receptor tyrosine kinase. ARROW ( NCT03037385 , ongoing) was designed to evaluate pralsetinib efficacy and safety in patients with advanced RET-altered solid tumors. Twenty-nine patients with 12 different RET fusion-positive solid tumor types, excluding non-small-cell lung cancer and thyroid cancer, who had previously received or were not candidates for standard therapies, were enrolled. The most common RET fusion partners in 23 efficacy-evaluable patients were CCDC6 (26%), KIF5B (26%) and NCOA4 (13%). Overall response rate, the primary endpoint, was 57% (95% confidence interval, 35-77) among these patients. Responses were observed regardless of tumor type or RET fusion partner. Median duration of response, progression-free survival and overall survival were 12 months, 7 months and 14 months, respectively. The most common grade ≥3 treatment-related adverse events were neutropenia (31%) and anemia (14%). These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib's potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RET fusion-positive solid tumors.
Identifiants
pubmed: 35962206
doi: 10.1038/s41591-022-01931-y
pii: 10.1038/s41591-022-01931-y
pmc: PMC9388374
doi:
Substances chimiques
Pyrazoles
0
Pyridines
0
Pyrimidines
0
pralsetinib
0
Proto-Oncogene Proteins c-ret
EC 2.7.10.1
RET protein, human
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT03037385']
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1640-1645Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA242845
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000371
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA180964
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA273168
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s).
Références
N Engl J Med. 2018 Jan 11;378(2):113-125
pubmed: 29151359
Ann Oncol. 2019 Dec 1;30(12):1856-1883
pubmed: 31549998
N Engl J Med. 2020 Aug 27;383(9):813-824
pubmed: 32846060
Oncotarget. 2015 Oct 6;6(30):28929-37
pubmed: 26078337
Nat Med. 2012 Feb 12;18(3):375-7
pubmed: 22327624
Cancer Discov. 2020 Apr;10(4):498-505
pubmed: 32094155
Nat Rev Drug Discov. 2020 Jun;19(6):383-384
pubmed: 32494047
N Engl J Med. 2010 Jun 24;362(25):2380-8
pubmed: 20573926
N Engl J Med. 2011 May 12;364(19):1817-25
pubmed: 21561347
Nat Commun. 2018 Nov 16;9(1):4821
pubmed: 30446652
Lancet Diabetes Endocrinol. 2021 Aug;9(8):491-501
pubmed: 34118198
Ann Oncol. 2016 Sep;27(suppl 5):v1-v27
pubmed: 27664245
Cancer Discov. 2018 Jul;8(7):836-849
pubmed: 29657135
Endocrinology. 2007 Mar;148(3):936-41
pubmed: 16946010
Clin Cancer Res. 2017 Apr 15;23(8):1988-1997
pubmed: 27683183
Nat Med. 2012 Feb 12;18(3):382-4
pubmed: 22327622
Clin Cancer Res. 2021 Aug 1;27(15):4160-4167
pubmed: 34088726
N Engl J Med. 2017 Aug 31;377(9):829-838
pubmed: 28586279
N Engl J Med. 2010 Apr 8;362(14):1273-81
pubmed: 20375404
N Engl J Med. 2013 Oct 31;369(18):1691-703
pubmed: 24131140
Lancet Oncol. 2021 Jul;22(7):959-969
pubmed: 34118197