Annual Meeting Proceedings Part 1 - American Society of Clinical ...

4107 General Poster Session (Board #49B), Mon, 8:00 AM-12:00 PM
Treatment of advanced or metastatic hepatocellular cancer (HCC): Final
clinical results of a single-arm phase II study of bevacizumab and
everolimus. Presenting Author: Gerhard Treiber, Department of Internal
Medicine, Zollernalb Clinic, Balingen, Germany
Background: mTOR inhibitors are emerging drugs for treatment (Tx) of
advanced hepatocellular cancer (HCC), their therapeutic effects may be
potentiated by combination with anti-VEGF partners (Treiber G, Expert Rev
Anticancer Ther 2009). Methods: Pts with histologically confirmed advanced
HCC were included. Tx consisted of RAD001 in a daily start dose of
5 mg orally and bevacizumab 5mg/kg iv every 2 weeks, up to 24 weeks.
Primary endpoint was TTP, secondary endpoints were OS, RR, changes in
biomarkers, and safety and tolerability besides PK analysis. Pts with either
a CPT Score � 9, a CLIP score � 3, or a Performance Status of ECOG � 2
were not eligible. Radiological TTP was centrally evaluated by both,
conventional(c)-, and modified(m)-RECIST criteria on a PP basis. Additionally,
we included a combined endpoint (TTPcomb: time to either clinical or
radiological progression leading to termination of treatment) as assessed by
the local centers in all recruited patients. Results: 33 pts (ITT) were
recruited (26 with Child A, 7 with Child B; median CLIP score was 2, mean
age 67 y, and mean BMI 28). 17/33 pts. had previous Tx (including
sorafenib � 3 months). Drop out other than PD was due to consent
withdrawl, lost to FU, and AE (n�5), therefore 28 patients had received
study medication �2 wks (PP). There were 65 CTC-AE grade 3/4 events
occuring in 22 pts. Median Tx duration was 69 days on RAD001, and a
median of 5 cycles of bevacizumab were applied. Dose adjustements for
RAD001 were performed in 20 pts, mean cumulative individual RAD dose
was 334 mg, there was no association between Cmin of RAD and TTP or
OS. On ITT, median TTPcomb was 2.0 mo and median OS was 9.0 mo. On
PP, median TTP approached 3.8 mo (conventional RECIST) and median
OS 9.7 mo. Using (m)RECIST, 5 pts. achieved PR within the first 8 wks,
and this was accompanied by a significant VEGF plasma decrease (median
of -65%), on (c)RECIST best response seen was SD. Conclusions: Combination
Tx of RAD001 and bevazicumab is tolerated acceptably. TTP and OS in
our 1°/2°-line HCC patients on Tx is comparable to sorafenib monotherapy
in the SHARP trial (1° line only).
4109 General Poster Session (Board #49D), Mon, 8:00 AM-12:00 PM
Biliary tract cancer: A large institutional experience. Presenting Author:
Mairead Geraldine McNamara, Princess Margaret Hospital, Toronto, ON,
Canada
Background: Biliary tract cancers (BTCs) encompass both cholangiocarcinoma
(CC), arising in intrahepatic, perihilar (klatskin), or distal biliary tree,
ampulla of vater and gallbladder carcinoma (GBC). Prognosis is poor for
majority of these patients (pts). Aim: To retrospectively review outcomes of
pts, as practices/treatments evolve, who presented to a multidisciplinary
team at tertiary referral center Princess Margaret Hospital, Toronto, with a
diagnosis of BTC. Methods: 1057 pts were followed from 01/87 - 09/11.
Complete demographics, performance status (PS), disease site, histological
diagnosis, percentage receiving surgery with curative intent, chemotherapy
(CT), radiotherapy (RT), recurrence patterns and overall survival
(OS) were analyzed. Results: The cohort includes 549 (52%) males, PS of
0-1 in 850 (80%), 2-3 in 87 (8%) pts. A histological diagnosis of
adenocarcinoma was confirmed in 885 (84%), 106 (10%) non diagnostic,
66 (6%) other. Definitive surgery was performed in 41% and adjuvant CT or
concurrent CT/RT given in 20% and 8% respectively. CT or CT/RT was
given for unresectable/metastatic disease in first line palliative setting in
395 (37%) and 18 pts (5%) respectively. Response to first line CT in GBC
was 33% vs. 24% in CC (p�0.005) and med survival was 8.4 and 13.1 mo
respectively (p�0.001). The OS for entire cohort of 1057 pts was 19.3 mo
with survival for breakdown of tumor type, stage detailed in the table. At
this time, 207 (20%) are still alive, 609 (58%) deceased, status unknown/
pending in 241 (22%). Conclusions: This represents a large biliary cancer
cohort with survival benchmarks obtained in modern era of multidisciplinary
care. Different subsites clearly present at different stages and have
different prognosis with treatments. Despite better responses for advanced
disease on CT in GBC, survival was better in CC consistent with reported
literature. Therapeutic advancement mandates finding additional drug
options and appropriate adjuvant care.
Location N (%)
Stage I
(%)
Stage II
(%)
Stage III
(%)
Stage IV
(%)
Median
survival
(mo)
Gallbladder 304 (29) 8 12 17 63 13.0
Distal bile duct 248 (23) 32 32 6 30 22.2
Ampulla of vater 186 (18) 51 23 13 13 46.8
Klatskin 162 (15) 14 10 24 52 16.5
Intrahepatic 157 (15) 13 18 10 59 20.4
Overall 1,057 (100) 19.3
Gastrointestinal (Noncolorectal) Cancer
265s
4108 General Poster Session (Board #49C), Mon, 8:00 AM-12:00 PM
A phase I/II study of foretinib, an oral multikinase inhibitor targeting MET,
RON, AXL, TIE-2, and VEGFR in advanced hepatocellular carcinoma
(HCC). Presenting Author: Thomas Cheung Yau, Department of Surgery,
The University of Hong Kong, Hong Kong, China
Background: Hepatocyte growth factor (HGF)/MET signalling plays a pivotal
role in tumor cell proliferation, migration and invasion in HCC and
circulating levels of HGF correlate with poor prognosis. This phase I/II trial
(MET111645) evaluated foretinib, an oral multikinase inhibitor targeting
MET, RON, AXL, TIE-2 and VEGFR, as first-line therapy in Asian advanced-
HCC patients. Methods: Asian patients with measurable, unresectable/
metastatic HCC, no prior sorafenib or other multi-kinase inhibitors, ECOG
PS 0-1, adequate organ function and Child-Pugh grade A were recruited.
The phase I was a standard 3�3 dose escalation design with a phase II
cohort expansion. The primary endpoint was safety and tolerability at the
maximum tolerated dose (MTD) and the secondary endpoints included
antitumor activity (objective response rate [ORR], disease stabilization rate
[DSR; confirmed CR/PR or SD for at least 12 weeks], and time to
progression [TTP] evaluated by central review according to modified
RECIST), and overall survival (OS) at the MTD, plus pharmacokinetics
(PK). Results: Thirteen patients were enrolled in phase I. Two dose-limiting
toxicities (DLT) (renal failure, proteinuria) were observed at 45 mg once
daily (QD) but no DLTs were observed at 30 mg QD. Thus, the MTD was
determined to be 30 mg QD. A further 32 patients were enrolled at the
MTD, for a study total of 39 patients treated at 30 mg QD. The most
common AEs, independent of causality,were hypertension (36%), decreased
appetite (23%), and pyrexia (21%). The most common SAEs were
hepatic encephalopathy (10%) and ascites (8%). Two patients discontinued
foretinib due to AEs. No dose reductions were reported. Thirty-eight
patients were evaluable for efficacy. The ORR was 24% (95% CI 11-40),
DSR 79% (95% CI; 63-90), and the median TTP was 4.2 months (95% CI
2.7-7.5). Mature OS data will be presented. Mean steady-state exposures
(AUC/Cmax) were comparable after administration of foretinib at 30 and 45
mg. Conclusions: Foretinib has an acceptable safety, tolerability, and PK
profile in an Asian HCC population. It has demonstrated promising
antitumor activity that warrants further testing in a randomized setting.
4110 General Poster Session (Board #49E), Mon, 8:00 AM-12:00 PM
Adjuvant chemotherapy following curative intent hepatectomy for intrahepatic
cholangiocarcinoma: Results from a multi-institutional analysis of
575 patients. Presenting Author: Dario Ribero, Ospedale Mauriziano,
Torino, Italy
Background: Surgical resection alone is the standard of care for patients
with resectable intrahepatic cholangiocarcinoma (IHC). This study evaluates
the benefit of adjuvant chemotherapy ( AdjCTx) following curative intent
hepatectomy for IHC. Methods: Clinicopathologic and long-term outcome
data of 575 consecutive patients treated with curative intent hepatectomy
for IHC (1995-2011) were extracted from a multi-institutional registry.
After excluding operative mortality and M1 (n�46), Cox regression analysis
was used to identify independent determinants of early recurrence (i.e.,
within 3 years). Propensity scores, which are used in observational studies
to reduce selection bias by equating groups on the basis of relevant
covariates, were calculated and utilized to match patients who had or had
not AdjCTx (one-to-one match). Cases whose propensity score deviated more
than 0.10 were considered unmatched and excluded from the analysis.
Primary end-point was recurrence-free survival (RFS) at 3-years. Results: At
a median FU of 42 months, 247 patients had recurred. Predictors of
recurrence were LN metastases (HR 1.83 [1.36-2.44]), radical resection
(HR 0.64 [0.45-0.9]), an elevated preoperative CA19.9 (HR 1.54 [1.15-
2.07]), vascular invasion (HR 1.97 [1.49-2.61]), multiple tumors (HR
2.21 [1.71-2.86]), and size (analysed as continuous variable) (HR 1.01
[1.01-1.01]). After matching, no difference was observed between patients
who had or had not AdjCTx (n�155 per group; 3-yrs RFS 28.3% vs. 38.0%,
respectively; p�NS). When the analysis was restricted to patients who had
gemcitabine, GEMOX or FOLFOX for 3 or more cycles (n�64 per group)
again no difference emerged between patients who had or had not AdjCTx
(3-yrs RFS 27.7% vs. 40.0% respectively, p�NS ). Conclusions: Our data
suggest that AdjCTx following resection of IHC does not increase 3-years
RFS.
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