Faculty Collaboration Database

Exploring response signals and targets in aggressive unresectable hepatocellular carcinoma: an analysis of targeted therapy phase 1 trials. Oncotarget 2015 Sep 29;6(29):28453-62

Date

07/15/2015

Pubmed ID

26164085

Pubmed Central ID

PMC4695071

DOI

10.18632/oncotarget.4601

Scopus ID

2-s2.0-84944449976 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

PURPOSE: Patients with advanced hepatocellular carcinoma (HCC) have limited effective therapeutic options. Given the rapid advanced in drug development and emergence of novel agents, we analyzed the characteristics and outcomes of HCC patients treated on early phase trials with an emphasis on targeted therapies.

METHODS: We reviewed the records of consecutive HCC patients evaluated in the Phase I Clinical Trials Program at MD Anderson from March 2004.

RESULTS: Thirty-nine patients were not treated due to poor performance status (n = 22, 56%) and decision to pursue alternate therapies (n = 10, 27%). Of 61 treated patients (median age, 60 years; median prior therapies, 3), eight patients (13%) attained stable disease lasting ≥6 months; four (7%) had a partial response, mainly with anti-angiogenic or multikinase inhibitors. Median Phase I progression-free survival (PFS) was 2.6 months versus 4.4 months (p 0.019) and 4.1 months (p 0.27) for their first-, and second-line FDA-approved therapy. Molecular analysis showed frequent PTEN loss (10/19 patients, 53%) and P53 mutation (4/4 patients tested). On multivariate analysis, independent factors predicting shorter survival were white ethnicity/race (p 0.031), cirrhosis (p 0.016), and serum sodium (p 0.0013).

CONCLUSIONS: In our heavily-pretreated HCC patients, the phase I PFS was comparable to that of 2nd-line therapy, highlighting a potential role for clinical trials after progression on first-line therapy. The response rate (SD>6 months/PR) of 20% was observed with early signals of activity in regimens combining inhibitors of angiogenesis, multiple kinases and mTOR with preliminary molecular analysis revealing prevalence of PTEN loss.

Author List

Subbiah IM, Falchook GS, Kaseb AO, Hess KR, Tsimberidou AM, Fu S, Subbiah V, Hong DS, Naing A, Piha-Paul SA, Akmal O, Janku F, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Biomarkers, Tumor
Carcinoma, Hepatocellular
Child
Clinical Trials, Phase I as Topic
Disease-Free Survival
Female
Humans
Liver Neoplasms
Male
Middle Aged
Molecular Targeted Therapy
Multivariate Analysis
Mutation
Prognosis
Young Adult