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

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: A/D met its predefined OS end point in patients with platinum-refractory mUC in this phase II trial. This trial is hypothesis generating requiring further study before informing practice.

Full Text

Duke Authors

Cited Authors

  • Rosenberg, JE; Hahn, NM; Regan, MM; Werner, L; Alva, A; George, S; Picus, J; Alter, R; Balar, A; Hoffman-Censits, J; Grivas, P; Lauer, R; Guancial, EA; Hoimes, C; Sonpavde, G; Albany, C; Stein, MN; Breen, T; Jacobs, C; Anderson, K; Bellmunt, J; Lalani, A-KA; Pal, S; Choueiri, TK

Published Date

  • May 2018

Published In

Volume / Issue

  • 118 / 11

Start / End Page

  • 1434 - 1441

PubMed ID

  • 29765151

Pubmed Central ID

  • PMC5988804

Electronic International Standard Serial Number (EISSN)

  • 1532-1827

Digital Object Identifier (DOI)

  • 10.1038/s41416-018-0087-9

Language

  • eng

Conference Location

  • England