Everolimus and pasireotide for advanced and metastatic hepatocellular carcinoma

Hanna K. Sanoff, Richard Kim, Anastasia Ivanova, Angela Alistar, Autumn J. McRee, Bert H. O'Neil

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: Few treatment options are available for patients with advanced or metastatic hepatocellular carcinoma (HCC). Based on preclinical and early clinical efficacy signals and lack of overlapping toxicity, we undertook this multicenter phase II trial to estimate efficacy and safety of everolimus and pasireotide in advanced HCC. Methods: Patients with advanced HCC not amenable to locoregional therapy and Child-Pugh A cirrhosis received everolimus 7.5 mg PO daily and pasireotide LAR 60 mg IM every 28 days. The primary endpoint was time to progression (TTP), with 26 events needed to evaluate if everolimus + pasireotide improved TTP from 2.8 to 4.4 months, with 80 % power and an alpha of 0.05. Secondary endpoints included response as measured by RECIST modified for HCC, treatment-emergent adverse events, and overall survival. Results: After 24 patients were enrolled, results of a randomized trial showing no benefit of everolimus in HCC were released prompting an unplanned interim analysis that found the conditional probability of rejecting the null hypothesis based on events in those patients was 0.08. Therefore accrual was halted. Patients had a median age of 59 years, 21 (88 %) had BCLC stage C cancer, and 11 (46 %) metastatic disease. Median TTP was 3.5 months (95 % CI 2-5.8) and median survival 6.7 months (95 % CI 6-infinity). Best response was stable disease in ten patients. Grade 3 hyperglycemia occurred in 6 (25 %). There were no grade 4 treatment-emergent events. Conclusion: Despite promising early efficacy signals, we found no benefit for the combination of everolimus and pasireotide in HCC.

Original languageEnglish (US)
Pages (from-to)505-509
Number of pages5
JournalInvestigational New Drugs
Volume33
Issue number2
DOIs
StatePublished - Apr 1 2015

Fingerprint

Hepatocellular Carcinoma
Survival
Therapeutics
Hyperglycemia
Everolimus
pasireotide
Fibrosis
Safety
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Sanoff, Hanna K. ; Kim, Richard ; Ivanova, Anastasia ; Alistar, Angela ; McRee, Autumn J. ; O'Neil, Bert H. / Everolimus and pasireotide for advanced and metastatic hepatocellular carcinoma. In: Investigational New Drugs. 2015 ; Vol. 33, No. 2. pp. 505-509.
@article{7499ef5f7d4c43c6a57ca6ac1fa99154,
title = "Everolimus and pasireotide for advanced and metastatic hepatocellular carcinoma",
abstract = "Purpose: Few treatment options are available for patients with advanced or metastatic hepatocellular carcinoma (HCC). Based on preclinical and early clinical efficacy signals and lack of overlapping toxicity, we undertook this multicenter phase II trial to estimate efficacy and safety of everolimus and pasireotide in advanced HCC. Methods: Patients with advanced HCC not amenable to locoregional therapy and Child-Pugh A cirrhosis received everolimus 7.5 mg PO daily and pasireotide LAR 60 mg IM every 28 days. The primary endpoint was time to progression (TTP), with 26 events needed to evaluate if everolimus + pasireotide improved TTP from 2.8 to 4.4 months, with 80 {\%} power and an alpha of 0.05. Secondary endpoints included response as measured by RECIST modified for HCC, treatment-emergent adverse events, and overall survival. Results: After 24 patients were enrolled, results of a randomized trial showing no benefit of everolimus in HCC were released prompting an unplanned interim analysis that found the conditional probability of rejecting the null hypothesis based on events in those patients was 0.08. Therefore accrual was halted. Patients had a median age of 59 years, 21 (88 {\%}) had BCLC stage C cancer, and 11 (46 {\%}) metastatic disease. Median TTP was 3.5 months (95 {\%} CI 2-5.8) and median survival 6.7 months (95 {\%} CI 6-infinity). Best response was stable disease in ten patients. Grade 3 hyperglycemia occurred in 6 (25 {\%}). There were no grade 4 treatment-emergent events. Conclusion: Despite promising early efficacy signals, we found no benefit for the combination of everolimus and pasireotide in HCC.",
author = "Sanoff, {Hanna K.} and Richard Kim and Anastasia Ivanova and Angela Alistar and McRee, {Autumn J.} and O'Neil, {Bert H.}",
year = "2015",
month = "4",
day = "1",
doi = "10.1007/s10637-015-0209-7",
language = "English (US)",
volume = "33",
pages = "505--509",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "2",

}

Everolimus and pasireotide for advanced and metastatic hepatocellular carcinoma. / Sanoff, Hanna K.; Kim, Richard; Ivanova, Anastasia; Alistar, Angela; McRee, Autumn J.; O'Neil, Bert H.

In: Investigational New Drugs, Vol. 33, No. 2, 01.04.2015, p. 505-509.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Everolimus and pasireotide for advanced and metastatic hepatocellular carcinoma

AU - Sanoff, Hanna K.

AU - Kim, Richard

AU - Ivanova, Anastasia

AU - Alistar, Angela

AU - McRee, Autumn J.

AU - O'Neil, Bert H.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Purpose: Few treatment options are available for patients with advanced or metastatic hepatocellular carcinoma (HCC). Based on preclinical and early clinical efficacy signals and lack of overlapping toxicity, we undertook this multicenter phase II trial to estimate efficacy and safety of everolimus and pasireotide in advanced HCC. Methods: Patients with advanced HCC not amenable to locoregional therapy and Child-Pugh A cirrhosis received everolimus 7.5 mg PO daily and pasireotide LAR 60 mg IM every 28 days. The primary endpoint was time to progression (TTP), with 26 events needed to evaluate if everolimus + pasireotide improved TTP from 2.8 to 4.4 months, with 80 % power and an alpha of 0.05. Secondary endpoints included response as measured by RECIST modified for HCC, treatment-emergent adverse events, and overall survival. Results: After 24 patients were enrolled, results of a randomized trial showing no benefit of everolimus in HCC were released prompting an unplanned interim analysis that found the conditional probability of rejecting the null hypothesis based on events in those patients was 0.08. Therefore accrual was halted. Patients had a median age of 59 years, 21 (88 %) had BCLC stage C cancer, and 11 (46 %) metastatic disease. Median TTP was 3.5 months (95 % CI 2-5.8) and median survival 6.7 months (95 % CI 6-infinity). Best response was stable disease in ten patients. Grade 3 hyperglycemia occurred in 6 (25 %). There were no grade 4 treatment-emergent events. Conclusion: Despite promising early efficacy signals, we found no benefit for the combination of everolimus and pasireotide in HCC.

AB - Purpose: Few treatment options are available for patients with advanced or metastatic hepatocellular carcinoma (HCC). Based on preclinical and early clinical efficacy signals and lack of overlapping toxicity, we undertook this multicenter phase II trial to estimate efficacy and safety of everolimus and pasireotide in advanced HCC. Methods: Patients with advanced HCC not amenable to locoregional therapy and Child-Pugh A cirrhosis received everolimus 7.5 mg PO daily and pasireotide LAR 60 mg IM every 28 days. The primary endpoint was time to progression (TTP), with 26 events needed to evaluate if everolimus + pasireotide improved TTP from 2.8 to 4.4 months, with 80 % power and an alpha of 0.05. Secondary endpoints included response as measured by RECIST modified for HCC, treatment-emergent adverse events, and overall survival. Results: After 24 patients were enrolled, results of a randomized trial showing no benefit of everolimus in HCC were released prompting an unplanned interim analysis that found the conditional probability of rejecting the null hypothesis based on events in those patients was 0.08. Therefore accrual was halted. Patients had a median age of 59 years, 21 (88 %) had BCLC stage C cancer, and 11 (46 %) metastatic disease. Median TTP was 3.5 months (95 % CI 2-5.8) and median survival 6.7 months (95 % CI 6-infinity). Best response was stable disease in ten patients. Grade 3 hyperglycemia occurred in 6 (25 %). There were no grade 4 treatment-emergent events. Conclusion: Despite promising early efficacy signals, we found no benefit for the combination of everolimus and pasireotide in HCC.

UR - http://www.scopus.com/inward/record.url?scp=84939951777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939951777&partnerID=8YFLogxK

U2 - 10.1007/s10637-015-0209-7

DO - 10.1007/s10637-015-0209-7

M3 - Article

VL - 33

SP - 505

EP - 509

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 2

ER -