A Randomized, Double-Blinded, Phase II Trial of Carboplatin and Pemetrexed with or without Apatorsen (OGX-427) in Patients with Previously Untreated Stage IV Non-Squamous-Non-Small-Cell Lung Cancer: The SPRUCE Trial.
Heat‐shock protein 27
Non‐small cell lung cancer
Oligonucleotide
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
17
08
2018
accepted:
20
02
2019
pubmed:
20
8
2019
medline:
2
9
2020
entrez:
18
8
2019
Statut:
ppublish
Résumé
This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein (Hsp) 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). Patients were randomized 1:1 to Arm A (carboplatin/pemetrexed plus apatorsen) or Arm B (carboplatin/pemetrexed plus placebo). Treatment was administered in 21-day cycles, with restaging every two cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and during treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, and toxicity. The trial enrolled 155 patients (median age 66 years; 44% Eastern Cooperative Oncology Group performance status 0). Toxicities were similar in the 2 treatment arms; cytopenias, nausea, vomiting, and fatigue were the most frequent treatment-related adverse events. Median PFS and OS were 6.0 and 10.8 months, respectively, for Arm A, and 4.9 and 11.8 months for Arm B (differences not statistically significant). Overall response rates were 27% for Arm A and 32% for Arm B. Sixteen patients (12%) had high serum levels of Hsp27 at baseline. In this small group, patients who received apatorsen had median PFS of 10.8 months, and those who received placebo had median PFS 4.8 months. The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting. This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting.
Sections du résumé
BACKGROUND
This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein (Hsp) 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC).
METHODS
Patients were randomized 1:1 to Arm A (carboplatin/pemetrexed plus apatorsen) or Arm B (carboplatin/pemetrexed plus placebo). Treatment was administered in 21-day cycles, with restaging every two cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and during treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, and toxicity.
RESULTS
The trial enrolled 155 patients (median age 66 years; 44% Eastern Cooperative Oncology Group performance status 0). Toxicities were similar in the 2 treatment arms; cytopenias, nausea, vomiting, and fatigue were the most frequent treatment-related adverse events. Median PFS and OS were 6.0 and 10.8 months, respectively, for Arm A, and 4.9 and 11.8 months for Arm B (differences not statistically significant). Overall response rates were 27% for Arm A and 32% for Arm B. Sixteen patients (12%) had high serum levels of Hsp27 at baseline. In this small group, patients who received apatorsen had median PFS of 10.8 months, and those who received placebo had median PFS 4.8 months.
CONCLUSION
The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting.
IMPLICATIONS FOR PRACTICE
This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting.
Identifiants
pubmed: 31420467
pii: theoncologist.2018-0518
doi: 10.1634/theoncologist.2018-0518
pmc: PMC6975937
doi:
Substances chimiques
Oligonucleotides
0
Pemetrexed
04Q9AIZ7NO
Carboplatin
BG3F62OND5
apatorsen
IFJ6X26JW6
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1409-e1416Informations de copyright
© AlphaMed Press 2019.
Déclaration de conflit d'intérêts
Disclosures of potential conflicts of interest may be found at the end of this article.
Références
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Ann Oncol. 2016 Jun;27(6):1116-22
pubmed: 27022067
Springerplus. 2016 Jul 25;5(1):1165
pubmed: 27512624
Pancreas. 2015 Oct;44(7):1121-9
pubmed: 26348464
Cell Cycle. 2006 Nov;5(22):2592-601
pubmed: 17106261
Anticancer Res. 2012 Jun;32(6):2295-9
pubmed: 22641665
Mol Cancer Ther. 2007 Jan;6(1):299-308
pubmed: 17218637
Cell Stress Chaperones. 2005 Summer;10(2):86-103
pubmed: 16038406
CA Cancer J Clin. 2015 Mar;65(2):87-108
pubmed: 25651787
Mol Cancer Ther. 2015 May;14(5):1107-16
pubmed: 25740245
CA Cancer J Clin. 2017 Jan;67(1):7-30
pubmed: 28055103
Cell Death Dis. 2011 Oct 20;2:e221
pubmed: 22012255
J Clin Oncol. 2009 Jul 1;27(19):3217-24
pubmed: 19433683
Oncologist. 2017 Dec;22(12):1427-e129
pubmed: 28935773
Cancer Res. 2004 Sep 15;64(18):6595-602
pubmed: 15374973
Curr Drug Targets. 2014 Apr;15(4):423-31
pubmed: 24138636
J Cell Mol Med. 2015 Feb;19(2):340-50
pubmed: 25331547