Atrasentan in patients with advanced renal cell carcinoma

A phase 2 trial of the ECOG-ACRIN cancer research group (E6800)

Michael A Carducci, Judith Manola, Suresh G. Nair, Glenn Liu, Steven Rousey, Janice P. Dutcher, George Wilding

Research output: Contribution to journalArticle

Abstract

Background Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era. Methods and Materials Patients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy. Results From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71% of patients reported no grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90% confidence interval) were 14% (6-25), 0% (0-39), 8% (1-23), and 22% (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95% confidence interval, 2.0-3.5 months). Conclusion Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.

Original languageEnglish (US)
Pages (from-to)531-539e1
JournalClinical Genitourinary Cancer
Volume13
Issue number6
DOIs
StatePublished - Dec 1 2015

Fingerprint

Renal Cell Carcinoma
Immunotherapy
Research
Neoplasms
Bone and Bones
Dyspnea
atrasentan
Confidence Intervals
Neoplasm Metastasis
Neutropenia
Vascular Endothelial Growth Factor A
Disease-Free Survival
Cardiac Arrhythmias
Thrombosis
Therapeutics
Drug Therapy

Keywords

  • Bone metastases
  • Endothelin A receptor antagonist
  • Kidney cancer
  • Pain palliation
  • Progression-free survival

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Atrasentan in patients with advanced renal cell carcinoma : A phase 2 trial of the ECOG-ACRIN cancer research group (E6800). / Carducci, Michael A; Manola, Judith; Nair, Suresh G.; Liu, Glenn; Rousey, Steven; Dutcher, Janice P.; Wilding, George.

In: Clinical Genitourinary Cancer, Vol. 13, No. 6, 01.12.2015, p. 531-539e1.

Research output: Contribution to journalArticle

Carducci, Michael A ; Manola, Judith ; Nair, Suresh G. ; Liu, Glenn ; Rousey, Steven ; Dutcher, Janice P. ; Wilding, George. / Atrasentan in patients with advanced renal cell carcinoma : A phase 2 trial of the ECOG-ACRIN cancer research group (E6800). In: Clinical Genitourinary Cancer. 2015 ; Vol. 13, No. 6. pp. 531-539e1.
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abstract = "Background Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era. Methods and Materials Patients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25{\%} among patients treated with prior immunotherapy and 45{\%} among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy. Results From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71{\%} of patients reported no grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90{\%} confidence interval) were 14{\%} (6-25), 0{\%} (0-39), 8{\%} (1-23), and 22{\%} (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95{\%} confidence interval, 2.0-3.5 months). Conclusion Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.",
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AU - Carducci, Michael A

AU - Manola, Judith

AU - Nair, Suresh G.

AU - Liu, Glenn

AU - Rousey, Steven

AU - Dutcher, Janice P.

AU - Wilding, George

PY - 2015/12/1

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N2 - Background Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era. Methods and Materials Patients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy. Results From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71% of patients reported no grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90% confidence interval) were 14% (6-25), 0% (0-39), 8% (1-23), and 22% (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95% confidence interval, 2.0-3.5 months). Conclusion Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.

AB - Background Atrasentan, an oral endothelin receptor A antagonist, demonstrated phase 1 activity in patients with renal cell carcinoma (RCC). A phase 2 study was undertaken in patients with measurable or bone-only metastatic RCC in the pre-VEGF/TKI era. Methods and Materials Patients were stratified by disease status and prior immunotherapy. Eligible patients had no prior chemotherapy, 0 to 1 prior immunotherapies, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received atrasentan 10 mg per day until progression. The primary end point was progression-free (PF) rate at 6 months. Rates of 25% among patients treated with prior immunotherapy and 45% among patients with no prior immunotherapy were considered promising. A 2-stage design was used for cohorts without prior immunotherapy. Results From 2003 to 2005, 98 patients were registered. Median treatment duration was 9.9 weeks (range, 0.3-107 weeks). Toxicities were mild; 71% of patients reported no grade 3 or higher treatment-related events. Grade 4 events included neutropenia (n = 3), dyspnea (n = 2), thrombosis (n = 1), and arrhythmia (n = 1). Two grade 5 events (dyspnea and constitutional) were possibly treatment related. Six-month PF rates (90% confidence interval) were 14% (6-25), 0% (0-39), 8% (1-23), and 22% (8-44), respectively, for patients with prior immunotherapy/measurable disease (n = 44), prior immunotherapy/bone metastases (n = 6), no prior immunotherapy/measurable disease (n = 25), and no prior immunotherapy/bone metastases (n = 18). Median PF survival was 2.3 months (95% confidence interval, 2.0-3.5 months). Conclusion Although well tolerated, atrasentan did not yield 6-month PF rates supporting its use as first-line monotherapy in patients with advanced RCC.

KW - Bone metastases

KW - Endothelin A receptor antagonist

KW - Kidney cancer

KW - Pain palliation

KW - Progression-free survival

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