A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma

Jennifer J. Knox, Rui Qin, Jonathan R. Strosberg, Benjamin Tan, Andreas Kaubisch, Anthony B. El-Khoueiry, Tanios S. Bekaii-Saab, Steven R. Rousey, Helen X. Chen, Charles Erlichman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.

Original languageEnglish (US)
Pages (from-to)241-246
Number of pages6
JournalInvestigational New Drugs
Volume33
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Hepatocellular Carcinoma
Medical Futility
Mucositis
Drug-Related Side Effects and Adverse Reactions
Vascular Endothelial Growth Factor A
Fatigue
Bevacizumab
temsirolimus
Diarrhea
Appointments and Schedules
Survival
Liver
Therapeutics

Keywords

  • Bevacizumab
  • Hepatocellular carcinoma
  • Phase II
  • Temsirolimus

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology
  • Medicine(all)

Cite this

A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma. / Knox, Jennifer J.; Qin, Rui; Strosberg, Jonathan R.; Tan, Benjamin; Kaubisch, Andreas; El-Khoueiry, Anthony B.; Bekaii-Saab, Tanios S.; Rousey, Steven R.; Chen, Helen X.; Erlichman, Charles.

In: Investigational New Drugs, Vol. 33, No. 1, 2015, p. 241-246.

Research output: Contribution to journalArticle

Knox, JJ, Qin, R, Strosberg, JR, Tan, B, Kaubisch, A, El-Khoueiry, AB, Bekaii-Saab, TS, Rousey, SR, Chen, HX & Erlichman, C 2015, 'A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma', Investigational New Drugs, vol. 33, no. 1, pp. 241-246. https://doi.org/10.1007/s10637-014-0169-3
Knox, Jennifer J. ; Qin, Rui ; Strosberg, Jonathan R. ; Tan, Benjamin ; Kaubisch, Andreas ; El-Khoueiry, Anthony B. ; Bekaii-Saab, Tanios S. ; Rousey, Steven R. ; Chen, Helen X. ; Erlichman, Charles. / A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma. In: Investigational New Drugs. 2015 ; Vol. 33, No. 1. pp. 241-246.
@article{2c6711a93c9c4e18b4548651bdd80001,
title = "A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma",
abstract = "Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 {\%} and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.",
keywords = "Bevacizumab, Hepatocellular carcinoma, Phase II, Temsirolimus",
author = "Knox, {Jennifer J.} and Rui Qin and Strosberg, {Jonathan R.} and Benjamin Tan and Andreas Kaubisch and El-Khoueiry, {Anthony B.} and Bekaii-Saab, {Tanios S.} and Rousey, {Steven R.} and Chen, {Helen X.} and Charles Erlichman",
year = "2015",
doi = "10.1007/s10637-014-0169-3",
language = "English (US)",
volume = "33",
pages = "241--246",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "1",

}

TY - JOUR

T1 - A phase II trial of bevacizumab plus temsirolimus in patients with advanced hepatocellular carcinoma

AU - Knox, Jennifer J.

AU - Qin, Rui

AU - Strosberg, Jonathan R.

AU - Tan, Benjamin

AU - Kaubisch, Andreas

AU - El-Khoueiry, Anthony B.

AU - Bekaii-Saab, Tanios S.

AU - Rousey, Steven R.

AU - Chen, Helen X.

AU - Erlichman, Charles

PY - 2015

Y1 - 2015

N2 - Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.

AB - Background There is strong rationale to combine temsirolimus (TEM) with Bevacizumab (BEV) for patients with advanced HCC. Methods A modified two-stage Simon phase II trial was performed with plans to advance to stage 2 if more than 2 patients had confirmed PR or >18 patients were progression free at 6 months out of 25 in stage 1. Toxicity, PFS and overall survival were secondary endpoints. Eligible pts had advanced HCC, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR targeted agents. Patients were treated with temsirolimus 25 mg IV on Days 1, 8, 15, and 22 of a 28 day cycle and bevacizumab 10 mg/kg IV on Days 1 and 15 of the cycle. Results Twenty-eight eligible patients were enrolled, 26 evaluable receiving a median of 6.5 cycles (range 1-18). Drug related toxicities were common including cytopenias, fatigue, mucositis, diarrhea and mild bleeds. Dose reductions or discontinuation of TEM were common. Accrual closed for presumed futility after interim analysis of the first 25 evaluable patients showed only one PR and 16/25 were progression-free at 6 months. However, the final data update in March 2013 demonstrated 4 confirmed PRs, a 5th unconfirmed PR and 16 /26 progression-free at 6 months. Median PFS and OS were 7 and 14 months respectively. Conclusion This first-line HCC trial evaluating the BEV/TEM doublet reports an ORR of 19 % and OS of 14 months which is favorable but requires further study at a more optimized dose and schedule.

KW - Bevacizumab

KW - Hepatocellular carcinoma

KW - Phase II

KW - Temsirolimus

UR - http://www.scopus.com/inward/record.url?scp=84922079748&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922079748&partnerID=8YFLogxK

U2 - 10.1007/s10637-014-0169-3

DO - 10.1007/s10637-014-0169-3

M3 - Article

VL - 33

SP - 241

EP - 246

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 1

ER -