Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago, and California Consortia (NCI9322/PHL86).
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
11
08
2019
revised:
10
12
2019
accepted:
24
01
2020
pubmed:
30
1
2020
medline:
4
9
2021
entrez:
30
1
2020
Statut:
ppublish
Résumé
The relevance of the MET/hepatocyte growth factor pathway in endometrial cancer tumor biology supports the clinical evaluation of cabozantinib in this disease. PHL86/NCI#9322 (NCT01935934) is a single arm study that evaluated cabozantinib (60 mg once daily) in women with endometrial cancer with progression after chemotherapy. Coprimary endpoints were response rate and 12-week progression-free-survival (PFS). Patients with uncommon histology endometrial cancer (eg, carcinosarcoma and clear cell) were enrolled in a parallel exploratory cohort. A total of 102 patients were accrued. Among 36 endometrioid histology patients, response rate was 14%, 12-week PFS rate was 67%, and median PFS was 4.8 months. In serous cohort of 34 patients, response rate was 12%, 12-week PFS was 56%, and median PFS was 4.0 months. In a separate cohort of 32 patients with uncommon histology endometrial cancer (including carcinosarcoma), response rate was 6% and 12-week PFS was 47%. Six patients were on treatment for >12 months, including two for >30 months. Common cabozantinib-related toxicities (>30% patients) included hypertension, fatigue, diarrhea, nausea, and hand-foot syndrome. Gastrointestinal fistula/perforation occurred in four of 70 (6%) patients with serous/endometrioid cancer and five of 32 (16%) patients in exploratory cohort. We observed increased frequency of responses with somatic Cabozantinib has activity in serous and endometrioid histology endometrial cancer. These results support further evaluation in genomically characterized patient cohorts.
Identifiants
pubmed: 31992589
pii: 1078-0432.CCR-19-2576
doi: 10.1158/1078-0432.CCR-19-2576
pmc: PMC7269808
mid: NIHMS1554652
doi:
Substances chimiques
Anilides
0
Pyridines
0
cabozantinib
1C39JW444G
Banques de données
ClinicalTrials.gov
['NCT01935934']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2477-2486Subventions
Organisme : NCI NIH HHS
ID : HHSN261201100032C
Pays : United States
Organisme : NCI NIH HHS
ID : N01CM62203
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186644
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
Références
Cancer. 1998 Feb 1;82(3):520-30
pubmed: 9452270
Cancer Cell. 2017 Mar 13;31(3):411-423
pubmed: 28292439
J Clin Oncol. 2017 Feb 20;35(6):591-597
pubmed: 28199818
Cancer. 2016 Dec 15;122(24):3856-3864
pubmed: 27525386
Gynecol Oncol. 2013 Apr;129(1):22-7
pubmed: 23262204
J Natl Cancer Inst. 2014 Sep 10;106(9):
pubmed: 25214561
Gynecol Oncol. 2012 Dec;127(3):538-43
pubmed: 22922531
Gynecol Oncol. 2018 Aug;150(2):274-281
pubmed: 29804638
J Clin Oncol. 2001 Oct 15;19(20):4048-53
pubmed: 11600606
Gynecol Obstet Invest. 2003;55(3):173-7
pubmed: 12865598
Gynecol Oncol. 2014 Jun;133(3):537-41
pubmed: 24594074
Gynecol Oncol. 2015 Sep;138(3):507-12
pubmed: 26186911
Ann Oncol. 2017 Nov 1;28(11):2813-2819
pubmed: 29045520
Oncotarget. 2015 Apr 30;6(12):10634-45
pubmed: 25860936
N Engl J Med. 2015 Nov 5;373(19):1814-23
pubmed: 26406150
Clin Cancer Res. 2019 Jan 15;25(2):652-662
pubmed: 30327304
Ann Oncol. 2004 Aug;15(8):1173-8
pubmed: 15277255
Br J Cancer. 2012 Jun 5;106(12):2004-9
pubmed: 22617129
N Engl J Med. 2018 Jul 05;379(1):54-63
pubmed: 29972759
J Clin Oncol. 2013 Oct 10;31(29):3639-46
pubmed: 24002501
J Clin Oncol. 2011 Jun 1;29(16):2259-65
pubmed: 21537039
Clin Cancer Res. 2017 Apr 15;23(8):1988-1997
pubmed: 27683183
Cancer. 1997 Aug 15;80(4):741-7
pubmed: 9264358
Int J Gynecol Cancer. 2019 Jan 18;:
pubmed: 30659026
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
Clin Cancer Res. 2007 Dec 15;13(24):7487-95
pubmed: 18094433
Eur J Cancer. 2016 May;59:99-108
pubmed: 27017291
Radiother Oncol. 2015 Dec;117(3):559-81
pubmed: 26683800
J Pathol. 2003 Apr;199(4):471-8
pubmed: 12635138
Int J Gynecol Cancer. 2011 Feb;21(2):316-22
pubmed: 21734474
J Clin Oncol. 2007 Nov 20;25(33):5180-6
pubmed: 18024865
Genome Med. 2016 Oct 25;8(1):109
pubmed: 27782854
Cytokine. 2014 Aug;68(2):94-100
pubmed: 24845798
Lancet Oncol. 2019 May;20(5):711-718
pubmed: 30922731
Lancet Oncol. 2016 Jul;17(7):917-927
pubmed: 27279544
Gynecol Oncol. 2014 Dec;135(3):441-5
pubmed: 25312396
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Gynecol Oncol. 2015 Jul;138(1):18-23
pubmed: 25925990
J Mol Diagn. 2016 Nov;18(6):842-850
pubmed: 27770852
Sci Rep. 2015 Dec 22;5:18657
pubmed: 26689674
Int J Gynecol Cancer. 2013 Jun;23(5):929-34
pubmed: 23598889
Int J Cancer. 2017 Mar 15;140(6):1396-1404
pubmed: 27905110
Gynecol Oncol. 2014 Aug;134(2):274-80
pubmed: 24882554
Cancer. 2017 Jun 1;123(11):1979-1988
pubmed: 28192597