A randomized phase 2 study of temozolomide and bevacizumab or nab-paclitaxel, carboplatin, and bevacizumab in patients with unresectable stage IV melanoma: A North Central Cancer Treatment Group study, N0775

Lisa A. Kottschade, Vera Jean Suman, Domingo G. Perez, Robert R Mc Williams, Judith S Kaur, Thomas T. Amatruda, Francois J. Geoffroy, Howard M. Gross, Peter A Cohen, Anthony J. Jaslowski, Matthew L. Kosel, Svetomir Nenad Markovic

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Background: Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM). Methods: A phase 2 trial was conducted in chemotherapy-naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m2 on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab-paclitaxel (100 mg/m2, or 80 mg/m2 post-addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post-addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression-free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60%. Results: Ninety-three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8% (95% confidence interval: 21.1%-51.2%) for TB and 56.1% (90% confidence interval: 44.7%-70.4%) for ABC. Conclusions: The addition of bevacizumab to nab-paclitaxel and carboplatin shows promising activity despite tolerability issues. Cancer 2013.

Original languageEnglish (US)
Pages (from-to)586-592
Number of pages7
JournalCancer
Volume119
Issue number3
DOIs
StatePublished - Feb 1 2013

Fingerprint

temozolomide
Carboplatin
Melanoma
Neoplasms
Area Under Curve
Therapeutics
Confidence Intervals
Survival
Combination Drug Therapy
Vascular Endothelial Growth Factor A
Disease-Free Survival
Fatigue
130-nm albumin-bound paclitaxel
Bevacizumab
Thrombosis
Survival Rate

Keywords

  • chemotherapy
  • combination therapy
  • metastatic melanoma
  • unresectable metastatic melanoma
  • vascular endothelial growth factor inhibition

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A randomized phase 2 study of temozolomide and bevacizumab or nab-paclitaxel, carboplatin, and bevacizumab in patients with unresectable stage IV melanoma : A North Central Cancer Treatment Group study, N0775. / Kottschade, Lisa A.; Suman, Vera Jean; Perez, Domingo G.; Mc Williams, Robert R; Kaur, Judith S; Amatruda, Thomas T.; Geoffroy, Francois J.; Gross, Howard M.; Cohen, Peter A; Jaslowski, Anthony J.; Kosel, Matthew L.; Markovic, Svetomir Nenad.

In: Cancer, Vol. 119, No. 3, 01.02.2013, p. 586-592.

Research output: Contribution to journalArticle

@article{d7ddc31e7a5749d9a9e3d9ee95720a53,
title = "A randomized phase 2 study of temozolomide and bevacizumab or nab-paclitaxel, carboplatin, and bevacizumab in patients with unresectable stage IV melanoma: A North Central Cancer Treatment Group study, N0775",
abstract = "Background: Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM). Methods: A phase 2 trial was conducted in chemotherapy-naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m2 on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab-paclitaxel (100 mg/m2, or 80 mg/m2 post-addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post-addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression-free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60{\%}. Results: Ninety-three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8{\%} (95{\%} confidence interval: 21.1{\%}-51.2{\%}) for TB and 56.1{\%} (90{\%} confidence interval: 44.7{\%}-70.4{\%}) for ABC. Conclusions: The addition of bevacizumab to nab-paclitaxel and carboplatin shows promising activity despite tolerability issues. Cancer 2013.",
keywords = "chemotherapy, combination therapy, metastatic melanoma, unresectable metastatic melanoma, vascular endothelial growth factor inhibition",
author = "Kottschade, {Lisa A.} and Suman, {Vera Jean} and Perez, {Domingo G.} and {Mc Williams}, {Robert R} and Kaur, {Judith S} and Amatruda, {Thomas T.} and Geoffroy, {Francois J.} and Gross, {Howard M.} and Cohen, {Peter A} and Jaslowski, {Anthony J.} and Kosel, {Matthew L.} and Markovic, {Svetomir Nenad}",
year = "2013",
month = "2",
day = "1",
doi = "10.1002/cncr.27760",
language = "English (US)",
volume = "119",
pages = "586--592",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - A randomized phase 2 study of temozolomide and bevacizumab or nab-paclitaxel, carboplatin, and bevacizumab in patients with unresectable stage IV melanoma

T2 - A North Central Cancer Treatment Group study, N0775

AU - Kottschade, Lisa A.

AU - Suman, Vera Jean

AU - Perez, Domingo G.

AU - Mc Williams, Robert R

AU - Kaur, Judith S

AU - Amatruda, Thomas T.

AU - Geoffroy, Francois J.

AU - Gross, Howard M.

AU - Cohen, Peter A

AU - Jaslowski, Anthony J.

AU - Kosel, Matthew L.

AU - Markovic, Svetomir Nenad

PY - 2013/2/1

Y1 - 2013/2/1

N2 - Background: Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM). Methods: A phase 2 trial was conducted in chemotherapy-naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m2 on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab-paclitaxel (100 mg/m2, or 80 mg/m2 post-addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post-addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression-free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60%. Results: Ninety-three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8% (95% confidence interval: 21.1%-51.2%) for TB and 56.1% (90% confidence interval: 44.7%-70.4%) for ABC. Conclusions: The addition of bevacizumab to nab-paclitaxel and carboplatin shows promising activity despite tolerability issues. Cancer 2013.

AB - Background: Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM). Methods: A phase 2 trial was conducted in chemotherapy-naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m2 on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab-paclitaxel (100 mg/m2, or 80 mg/m2 post-addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post-addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression-free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60%. Results: Ninety-three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8% (95% confidence interval: 21.1%-51.2%) for TB and 56.1% (90% confidence interval: 44.7%-70.4%) for ABC. Conclusions: The addition of bevacizumab to nab-paclitaxel and carboplatin shows promising activity despite tolerability issues. Cancer 2013.

KW - chemotherapy

KW - combination therapy

KW - metastatic melanoma

KW - unresectable metastatic melanoma

KW - vascular endothelial growth factor inhibition

UR - http://www.scopus.com/inward/record.url?scp=84872956413&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872956413&partnerID=8YFLogxK

U2 - 10.1002/cncr.27760

DO - 10.1002/cncr.27760

M3 - Article

C2 - 22915053

AN - SCOPUS:84872956413

VL - 119

SP - 586

EP - 592

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 3

ER -