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

Jonathan E. Rosenberg, Noah M. Hahn, Meredith M. Regan, Lillian Werner, Ajjai Alva, Saby George, Joel Picus, Robert Alter, Arjun Balar, Jean Hoffman-Censits, Petros Grivas, Richard Lauer, Elizabeth A. Guancial, Christopher Hoimes, Guru Sonpavde, Costantine Albany, Mark N. Stein, Tim Breen, Cindy Jacobs, Kirsten AndersonJoaquim Bellmunt, Aly Khan A. Lalani, Sumanta Pal, Toni K. Choueiri

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1434-1441
Number of pages8
JournalBritish Journal of Cancer
Volume118
Issue number11
DOIs
StatePublished - May 1 2018

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docetaxel
Platinum
Carcinoma
Survival
Antisense Oligonucleotides
Random Allocation
Drug Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rosenberg, J. E., Hahn, N. M., Regan, M. M., Werner, L., Alva, A., George, S., ... Choueiri, T. K. (2018). Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2). British Journal of Cancer, 118(11), 1434-1441. https://doi.org/10.1038/s41416-018-0087-9

Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2). / 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, Costantine; Stein, Mark N.; Breen, Tim; Jacobs, Cindy; Anderson, Kirsten; Bellmunt, Joaquim; Lalani, Aly Khan A.; Pal, Sumanta; Choueiri, Toni K.

In: British Journal of Cancer, Vol. 118, No. 11, 01.05.2018, p. 1434-1441.

Research output: Contribution to journalArticle

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, AKA, Pal, S & Choueiri, TK 2018, 'Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)', British Journal of Cancer, vol. 118, no. 11, pp. 1434-1441. https://doi.org/10.1038/s41416-018-0087-9
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, Costantine ; Stein, Mark N. ; Breen, Tim ; Jacobs, Cindy ; Anderson, Kirsten ; Bellmunt, Joaquim ; Lalani, Aly Khan A. ; Pal, Sumanta ; Choueiri, Toni K. / Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2). In: British Journal of Cancer. 2018 ; Vol. 118, No. 11. pp. 1434-1441.
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abstract = "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.",
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T1 - Apatorsen plus docetaxel versus docetaxel alone in platinum-resistant metastatic urothelial carcinoma (Borealis-2)

AU - Rosenberg, Jonathan E.

AU - Hahn, Noah M.

AU - Regan, Meredith M.

AU - Werner, Lillian

AU - Alva, Ajjai

AU - George, Saby

AU - Picus, Joel

AU - Alter, Robert

AU - Balar, Arjun

AU - Hoffman-Censits, Jean

AU - Grivas, Petros

AU - Lauer, Richard

AU - Guancial, Elizabeth A.

AU - Hoimes, Christopher

AU - Sonpavde, Guru

AU - Albany, Costantine

AU - Stein, Mark N.

AU - Breen, Tim

AU - Jacobs, Cindy

AU - Anderson, Kirsten

AU - Bellmunt, Joaquim

AU - Lalani, Aly Khan A.

AU - Pal, Sumanta

AU - Choueiri, Toni K.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

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