Prognostic factors associated with treatment response to octreotide in advanced hepatocellular cancer (HCC)

Abstract

4185 Background: Results from clinical trials using octreotide for treatment of advanced HCC are conflicting. Current objective was to evaluate prognostic factors before and during treatment with Sandostatin LAR 30 mg (monthly). Methods: Prospective cohort of 75 patients. They were treated for a minimum of six months or until one final endpoint (progression or death) was reached. Optimal cut-offs were derived from ROC analysis. Results: (logrank tests): Progression within or later than 90 days of treatment was the best clinical decision making for longterm survival outcome (p<0.0001), median PFS was 468 days. A CLIP score > 2 decreased median survival from 230 to 113 days (p<0.01), okuda stage 3 was similiar. 79% of patients had an increased uptake by octreoscan (>1.5 fold than non-tumorous liver). An uptake <2 fold was associated with longer survival (median: 391 vs. 158 days, p=0.05), in patients evaluable during follow up, octreoscan uptake was unchanged in most cases. A prestudy serum VEGF-A value of >660 pg/ml shortened survival from 205 to 95 days (p <0.01). A decrease in VEGF-A by month 3 or 6 of treatment below a ratio of 0.7 was predictive best: by 2.5 years 45% of patients vs. 8% of patients survived (p=0.01). Other serum markers evaluated with significant differences in survival were soluble interleukin 2 receptor and osteopontin. Their corresponding cut-offs of 1310 pg/ml and 1060 U/l discriminated between 220–230 and 114 days of survival (p<0.01 each). In contrast to previous reports, serum IGF-1 was marginally associated with survival outcome in this study. Conclusions: Overall median time to progression (122 days) and median survival (153 days) in our study was short. However, for the first time, we are able to identify a subgroup of patients with no measurable HCC tumor progression and long-term survival due to treatment with octreotide. The most intriguing finding was the association between VEGF-A decline and treatment response, thus suggesting the inhibition of angiogenesis as the main factor of action for octreotide. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharma, Nueremberg, Germany