Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial.
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
Biomarkers, Tumor
/ genetics
Chemoradiotherapy
/ mortality
Female
Gene Expression Profiling
Humans
Male
Middle Aged
Neoplasm Metastasis
Neoplasms
/ genetics
Prognosis
Radiosurgery
/ mortality
Survival Rate
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:
15 12 2020
15 12 2020
Historique:
received:
13
05
2020
revised:
13
07
2020
accepted:
30
09
2020
pubmed:
9
10
2020
medline:
15
12
2021
entrez:
8
10
2020
Statut:
ppublish
Résumé
Multisite stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) has demonstrated safety in advanced solid tumors (ASTs). However, no studies have examined the relationships between irradiated tumor response, SBRT-induced tumor gene expression, and overall survival (OS). Patients with AST received SBRT (30-50 Gy in 3-5 fractions) to two to four metastases followed by pembrolizumab (200 mg i.v. every 3 weeks). SBRT was prescribed to a maximum tumor volume of 65 mL. Small metastases received the complete prescribed coverage (complete-Rx), while larger metastases received partial coverage (partial-Rx). Treated metastasis control (TMC) was defined as a lack of progression for an irradiated metastasis. Landmark analysis was used to assess the relationship between TMC and OS. Thirty-five biopsies were obtained from 24 patients: 19 pre-SBRT and 16 post-SBRT (11 matched) prior to pembrolizumab and were analyzed via RNA microarray. Sixty-eight patients (139 metastases) were enrolled with a median follow-up of 10.4 months. One-year TMC was 89.5% with no difference between complete-Rx or partial-Rx. On multivariable analysis, TMC was independently associated with a reduced risk for death (HR, 0.36; 95% confidence interval, 0.17-0.75; In the context of SBRT+P, TMC independently correlates with OS. SBRT impacts intratumoral immune gene expression associated with TMC. Randomized trials are needed to validate these findings.
Identifiants
pubmed: 33028595
pii: 1078-0432.CCR-20-1790
doi: 10.1158/1078-0432.CCR-20-1790
pmc: PMC8561652
mid: NIHMS1635960
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
pembrolizumab
DPT0O3T46P
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6437-6444Subventions
Organisme : NCI NIH HHS
ID : K12 CA139160
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014599
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024999
Pays : United States
Informations de copyright
©2020 American Association for Cancer Research.
Références
Cancer Cell. 2017 May 8;31(5):711-723.e4
pubmed: 28486109
Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):343-9
pubmed: 23462419
Cancer. 2012 Jun 1;118(11):2962-70
pubmed: 22020702
JAMA Oncol. 2020 May 1;6(5):650-659
pubmed: 32215577
Int J Radiat Oncol Biol Phys. 2021 May 1;110(1):188-195
pubmed: 29395629
Immunity. 2014 Nov 20;41(5):830-42
pubmed: 25517615
Nat Commun. 2017 Nov 23;8(1):1736
pubmed: 29170400
Nat Med. 2019 Apr;25(4):656-666
pubmed: 30833750
Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19386-91
pubmed: 23132945
Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):878-86
pubmed: 22172903
Radiother Oncol. 2017 Feb;122(2):286-294
pubmed: 27871671
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
Nat Rev Clin Oncol. 2017 Jun;14(6):365-379
pubmed: 28094262
Sci Signal. 2014 Sep 02;7(341):re5
pubmed: 25185158
Cancer Res. 2009 Apr 1;69(7):3077-85
pubmed: 19293190
Immunity. 2014 Nov 20;41(5):843-52
pubmed: 25517616
J Clin Oncol. 1983 Nov;1(11):710-9
pubmed: 6668489
Cell. 2015 Jan 15;160(1-2):48-61
pubmed: 25594174
Cancer Immunol Res. 2018 Sep;6(9):990-1000
pubmed: 30181337
J Neurosurg Spine. 2013 Mar;18(3):207-14
pubmed: 23339593
Cancer Res. 2011 Apr 1;71(7):2488-96
pubmed: 21300764
Nat Commun. 2017 Jun 09;8:15618
pubmed: 28598415
Lancet Oncol. 2019 Apr;20(4):494-503
pubmed: 30770291
Clin Cancer Res. 2018 Jun 1;24(11):2493-2504
pubmed: 29476019
J Clin Oncol. 2018 Jun 1;36(16):1611-1618
pubmed: 29437535
Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):112-8
pubmed: 18786780
Int J Radiat Oncol Biol Phys. 2019 Mar 1;103(3):697-708
pubmed: 30342090
Neurosurg Focus. 2017 Jan;42(1):E6
pubmed: 28041329
Nature. 2017 May 4;545(7652):60-65
pubmed: 28397821
J Clin Oncol. 2017 Aug 1;35(22):2535-2541
pubmed: 28489510
Cancer. 2016 Jul 15;122(14):2242-50
pubmed: 27206146
Cancer Res. 1993 Sep 1;53(17):3880-6
pubmed: 8358713
Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1193-9
pubmed: 23332384
J Clin Oncol. 2009 Apr 1;27(10):1579-84
pubmed: 19255320
J Thorac Oncol. 2007 Jul;2(7 Suppl 3):S94-100
pubmed: 17603311
Radiat Oncol. 2018 Feb 13;13(1):26
pubmed: 29439707
J Cancer. 2010 Jun 28;1:80-92
pubmed: 20842228