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- Title
Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2).
- Authors
Rosenberg, Jonathan E.; Hahn, Noah M.; Regan, Meredith M.; Werner, Lillian; Alva, Ajjai; George, Saby; Picus, Joel; Alter, Robert; Balar, Arjun; Hoffman-Censits, Jean; Grivas, Petros; Lauer, Richard; Guancial, Elizabeth A.; Hoimes, Christopher; Sonpavde, Guru; Albany, Constantine; Stein, Mark N.; Breen, Tim; Jacobs, Cindy; Anderson, Kirsten
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
British Journal of Cancer, 2018, Vol 118, Issue 11, p1434
- ISSN
0007-0920
- Publication type
journal article
- DOI
10.1038/s41416-018-0087-9