Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

British Journal of Cancer
Jonathan E RosenbergToni K Choueiri

Abstract

A randomised study to assess the addition of apatorsen, an antisense oligonucleotide that inhibits Hsp27 expression, to docetaxel in patients with metastatic urothelial carcinoma (mUC) relapsed after prior platinum-based chemotherapy. Multicentre, phase II study with 1:1 randomisation to apatorsen (three loading doses at 600 mg intravenous followed by weekly doses) plus docetaxel (75 mg/m2 intravenous every 21 days) (A/D) or docetaxel alone. Overall survival (OS) was the primary end point with a P value <0.1 (one-sided) being positive. Progression-free survival (PFS), objective response rate (ORR), safety, and effect of Hsp27 levels on outcomes were secondary end points. Patients randomised to A/D (n = 99) had improved OS compared to docetaxel alone (n = 101): HR: 0.80, 80% CI: 0.65-0.98, P = 0.0784, median 6.4 vs 5.9 months. PFS and ORR were similar in both arms. A/D had more incidence of sepsis and urinary tract infections. Patients with baseline Hsp27 levels <5.7 ng/mL had improved OS compared to those with levels ≥5.7 ng/mL. Patients with a decline or ≤20.5% increase in Hsp27 from baseline benefited more from A/D than those with >20.5% increase. A/D met its predefined OS end point in patients with platinum-refractory mUC in...Continue Reading

References

Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A K DeC Miller-Graziano
Sep 7, 2002·International Journal of Cancer. Journal International Du Cancer·Heba Sh KassemGeoffrey P Margison
Nov 9, 2002·The Lancet Oncology·Burkhard Jansen, Uwe Zangemeister-Wittke
Oct 8, 2003·Current Cancer Drug Targets·Paul Workman
Oct 7, 2004·Cancer Biology & Therapy·Leticia B A RangelPatrice J Morin
Sep 22, 2005·Nature Reviews. Cancer·Luke Whitesell, Susan L Lindquist
Aug 19, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joaquim BellmuntHans von der Maase
Mar 17, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joaquim BellmuntJonathan E Rosenberg
Dec 21, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Toni K ChoueiriPhilip W Kantoff
May 17, 2012·Proceedings of the National Academy of Sciences of the United States of America·Oddbjørn StraumeGeorge N Naumov
May 15, 2013·Nature Reviews. Urology·Joseph Ischia, Alan I So
Feb 18, 2017·The New England Journal of Medicine·Joaquim BellmuntUNKNOWN KEYNOTE-045 Investigators
Sep 30, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J BellmuntD P Petrylak

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Citations

Nov 10, 2018·Expert Opinion on Pharmacotherapy·Aly-Khan A Lalani, Guru P Sonpavde
Oct 28, 2019·International Journal of Molecular Sciences·Maxim ShevtsovBoris Margulis
Jan 16, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Anna M Krichevsky, Erik J Uhlmann
Dec 24, 2018·Therapeutic Advances in Urology·Alfonso Gómez De Liaño, Ignacio Duran
Dec 18, 2019·The Journal of Clinical Investigation·Lucia NappiMartin Gleave
Oct 29, 2020·Cell Stress & Chaperones·Daniela CaporossiIvan Dimauro
Nov 12, 2020·BMJ Evidence-based Medicine·Eric A ApaydinSusanne Hempel
May 8, 2021·Hematology/oncology Clinics of North America·Rosa NadalJoaquim Bellmunt

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Methods Mentioned

BETA
antisense oligonucleotide
enzyme-linked immunosorbent assay

Software Mentioned

OnCore
CONSORT

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