Phase II trial of eribulin in patients with metastatic hormone refractory prostate cancer

A trial of the ECOG-ACRIN Cancer Research Group (E5805)

Mark Stein, Yu Hui Chen, Michael A. Carducci, Gary R. Hudes, Pauline M. Lerma, Winston W. Tan, Robert Dalune, Kendrith M. Rowland, Timothy M. Kuzel, Robert S. DiPaola

Research output: Contribution to journalArticle

Abstract

Background: Eribulin mesylate, a synthetic analog of halichondrin B, is a novel tubulin-binding agent that inhibits cancer cell proliferation at low-nanomolar levels. Methods: In a multicenter ECOG trial, patients with progressive metastatic CRPC, ECOG 0-2 were treated with eribulin 1.4 mg/m2 as an IV bolus over 5 minutes on days 1 and 8 of a 21-day cycle. This noncomparative study stratified points to either a chemonaive (CN), prior-taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The trial was powered to detect a 50% PSA reduction using Consensus Criteria in at least 40% versus 20% (90% power, one-sided α=0.10) for the CN stratum and 25% versus. 10% (power 87%, one-sided α=0.10) for the Tax and TCx strata. Results: In total, 119 pts received treatment of which 116 were eligible for the primary response determination in this study. Median age 70 years (range, 45 to 88); median number of treatment cycles 4 (range, 1 to 20+); ECOG 0-1 90%. Confirmed PSA response rates (50% decline from baseline) were 29% (90% [18.2%, 41.2%]; P=0.20), 10% (90% [5.2%, 27.1%]; P=1.00), and 4% ([0.2%, 18.3%]; P=0.59) in the chemonaive stratum, the prior-taxane stratum, and the 2-priorchemotherapy stratum, respectively. Median progression-free survival was 3.5 months (95% CI, 2.0, 5.9), 2.3 months (95% CI, 2.0, 2.9) and 3.7 months (95% CI, 2.1, 4.2) for the chemonaive stratum, the priortaxane stratum and the 2-prior-chemotherapy stratum, respectively. Nonhematological toxicities of any grade (mainly grade 1 and 2) were fatigue (74%), neuropathy (40%), alopecia (39%), nausea (35%), and anorexia (34%). Common hematological toxicities were decreased leukocytes (75%), decreased neutrophils (72%), and decreased hemoglobin (66%). The most common grade ≥ 3 toxicities were decreased neutrophils (55%), decreased leukocytes (42%), sensory neuropathy (13%), and fatigue (11%). Overall, there was a 4% rate of febrile neutropenia. Conclusions: In summary, per the prespecified study endpoints, eribulin did not have adequate activity in chemotherapy naïve or chemotherapy pretreated patients with metastatic CRPC to support further study in this setting.

Original languageEnglish (US)
Pages (from-to)375-381
Number of pages7
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume42
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

eribulin
Prostatic Neoplasms
Hormones
Drug Therapy
Research
Fatigue
Neoplasms
Neutrophils
Leukocytes
Febrile Neutropenia
Alopecia
Anorexia
Tubulin
Nausea
Multicenter Studies
Disease-Free Survival
Hemoglobins
Cell Proliferation
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Castrate resistant prostate cancer
  • Eribulin
  • Microtubule Inhibitor

Cite this

Stein, Mark ; Chen, Yu Hui ; Carducci, Michael A. ; Hudes, Gary R. ; Lerma, Pauline M. ; Tan, Winston W. ; Dalune, Robert ; Rowland, Kendrith M. ; Kuzel, Timothy M. ; DiPaola, Robert S. / Phase II trial of eribulin in patients with metastatic hormone refractory prostate cancer : A trial of the ECOG-ACRIN Cancer Research Group (E5805). In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2019 ; Vol. 42, No. 4. pp. 375-381.
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abstract = "Background: Eribulin mesylate, a synthetic analog of halichondrin B, is a novel tubulin-binding agent that inhibits cancer cell proliferation at low-nanomolar levels. Methods: In a multicenter ECOG trial, patients with progressive metastatic CRPC, ECOG 0-2 were treated with eribulin 1.4 mg/m2 as an IV bolus over 5 minutes on days 1 and 8 of a 21-day cycle. This noncomparative study stratified points to either a chemonaive (CN), prior-taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The trial was powered to detect a 50{\%} PSA reduction using Consensus Criteria in at least 40{\%} versus 20{\%} (90{\%} power, one-sided α=0.10) for the CN stratum and 25{\%} versus. 10{\%} (power 87{\%}, one-sided α=0.10) for the Tax and TCx strata. Results: In total, 119 pts received treatment of which 116 were eligible for the primary response determination in this study. Median age 70 years (range, 45 to 88); median number of treatment cycles 4 (range, 1 to 20+); ECOG 0-1 90{\%}. Confirmed PSA response rates (50{\%} decline from baseline) were 29{\%} (90{\%} [18.2{\%}, 41.2{\%}]; P=0.20), 10{\%} (90{\%} [5.2{\%}, 27.1{\%}]; P=1.00), and 4{\%} ([0.2{\%}, 18.3{\%}]; P=0.59) in the chemonaive stratum, the prior-taxane stratum, and the 2-priorchemotherapy stratum, respectively. Median progression-free survival was 3.5 months (95{\%} CI, 2.0, 5.9), 2.3 months (95{\%} CI, 2.0, 2.9) and 3.7 months (95{\%} CI, 2.1, 4.2) for the chemonaive stratum, the priortaxane stratum and the 2-prior-chemotherapy stratum, respectively. Nonhematological toxicities of any grade (mainly grade 1 and 2) were fatigue (74{\%}), neuropathy (40{\%}), alopecia (39{\%}), nausea (35{\%}), and anorexia (34{\%}). Common hematological toxicities were decreased leukocytes (75{\%}), decreased neutrophils (72{\%}), and decreased hemoglobin (66{\%}). The most common grade ≥ 3 toxicities were decreased neutrophils (55{\%}), decreased leukocytes (42{\%}), sensory neuropathy (13{\%}), and fatigue (11{\%}). Overall, there was a 4{\%} rate of febrile neutropenia. Conclusions: In summary, per the prespecified study endpoints, eribulin did not have adequate activity in chemotherapy na{\"i}ve or chemotherapy pretreated patients with metastatic CRPC to support further study in this setting.",
keywords = "Castrate resistant prostate cancer, Eribulin, Microtubule Inhibitor",
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Phase II trial of eribulin in patients with metastatic hormone refractory prostate cancer : A trial of the ECOG-ACRIN Cancer Research Group (E5805). / Stein, Mark; Chen, Yu Hui; Carducci, Michael A.; Hudes, Gary R.; Lerma, Pauline M.; Tan, Winston W.; Dalune, Robert; Rowland, Kendrith M.; Kuzel, Timothy M.; DiPaola, Robert S.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 42, No. 4, 01.04.2019, p. 375-381.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II trial of eribulin in patients with metastatic hormone refractory prostate cancer

T2 - A trial of the ECOG-ACRIN Cancer Research Group (E5805)

AU - Stein, Mark

AU - Chen, Yu Hui

AU - Carducci, Michael A.

AU - Hudes, Gary R.

AU - Lerma, Pauline M.

AU - Tan, Winston W.

AU - Dalune, Robert

AU - Rowland, Kendrith M.

AU - Kuzel, Timothy M.

AU - DiPaola, Robert S.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background: Eribulin mesylate, a synthetic analog of halichondrin B, is a novel tubulin-binding agent that inhibits cancer cell proliferation at low-nanomolar levels. Methods: In a multicenter ECOG trial, patients with progressive metastatic CRPC, ECOG 0-2 were treated with eribulin 1.4 mg/m2 as an IV bolus over 5 minutes on days 1 and 8 of a 21-day cycle. This noncomparative study stratified points to either a chemonaive (CN), prior-taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The trial was powered to detect a 50% PSA reduction using Consensus Criteria in at least 40% versus 20% (90% power, one-sided α=0.10) for the CN stratum and 25% versus. 10% (power 87%, one-sided α=0.10) for the Tax and TCx strata. Results: In total, 119 pts received treatment of which 116 were eligible for the primary response determination in this study. Median age 70 years (range, 45 to 88); median number of treatment cycles 4 (range, 1 to 20+); ECOG 0-1 90%. Confirmed PSA response rates (50% decline from baseline) were 29% (90% [18.2%, 41.2%]; P=0.20), 10% (90% [5.2%, 27.1%]; P=1.00), and 4% ([0.2%, 18.3%]; P=0.59) in the chemonaive stratum, the prior-taxane stratum, and the 2-priorchemotherapy stratum, respectively. Median progression-free survival was 3.5 months (95% CI, 2.0, 5.9), 2.3 months (95% CI, 2.0, 2.9) and 3.7 months (95% CI, 2.1, 4.2) for the chemonaive stratum, the priortaxane stratum and the 2-prior-chemotherapy stratum, respectively. Nonhematological toxicities of any grade (mainly grade 1 and 2) were fatigue (74%), neuropathy (40%), alopecia (39%), nausea (35%), and anorexia (34%). Common hematological toxicities were decreased leukocytes (75%), decreased neutrophils (72%), and decreased hemoglobin (66%). The most common grade ≥ 3 toxicities were decreased neutrophils (55%), decreased leukocytes (42%), sensory neuropathy (13%), and fatigue (11%). Overall, there was a 4% rate of febrile neutropenia. Conclusions: In summary, per the prespecified study endpoints, eribulin did not have adequate activity in chemotherapy naïve or chemotherapy pretreated patients with metastatic CRPC to support further study in this setting.

AB - Background: Eribulin mesylate, a synthetic analog of halichondrin B, is a novel tubulin-binding agent that inhibits cancer cell proliferation at low-nanomolar levels. Methods: In a multicenter ECOG trial, patients with progressive metastatic CRPC, ECOG 0-2 were treated with eribulin 1.4 mg/m2 as an IV bolus over 5 minutes on days 1 and 8 of a 21-day cycle. This noncomparative study stratified points to either a chemonaive (CN), prior-taxane (Tax) only, or 2 prior cytotoxic (TCx) chemotherapy arm. The trial was powered to detect a 50% PSA reduction using Consensus Criteria in at least 40% versus 20% (90% power, one-sided α=0.10) for the CN stratum and 25% versus. 10% (power 87%, one-sided α=0.10) for the Tax and TCx strata. Results: In total, 119 pts received treatment of which 116 were eligible for the primary response determination in this study. Median age 70 years (range, 45 to 88); median number of treatment cycles 4 (range, 1 to 20+); ECOG 0-1 90%. Confirmed PSA response rates (50% decline from baseline) were 29% (90% [18.2%, 41.2%]; P=0.20), 10% (90% [5.2%, 27.1%]; P=1.00), and 4% ([0.2%, 18.3%]; P=0.59) in the chemonaive stratum, the prior-taxane stratum, and the 2-priorchemotherapy stratum, respectively. Median progression-free survival was 3.5 months (95% CI, 2.0, 5.9), 2.3 months (95% CI, 2.0, 2.9) and 3.7 months (95% CI, 2.1, 4.2) for the chemonaive stratum, the priortaxane stratum and the 2-prior-chemotherapy stratum, respectively. Nonhematological toxicities of any grade (mainly grade 1 and 2) were fatigue (74%), neuropathy (40%), alopecia (39%), nausea (35%), and anorexia (34%). Common hematological toxicities were decreased leukocytes (75%), decreased neutrophils (72%), and decreased hemoglobin (66%). The most common grade ≥ 3 toxicities were decreased neutrophils (55%), decreased leukocytes (42%), sensory neuropathy (13%), and fatigue (11%). Overall, there was a 4% rate of febrile neutropenia. Conclusions: In summary, per the prespecified study endpoints, eribulin did not have adequate activity in chemotherapy naïve or chemotherapy pretreated patients with metastatic CRPC to support further study in this setting.

KW - Castrate resistant prostate cancer

KW - Eribulin

KW - Microtubule Inhibitor

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