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

306s Genitourinary Cancer
4618 General Poster Session (Board #7A), Sun, 8:00 AM-12:00 PM
Evaluation with DCE-US of antiangiogenic treatments in 539 patients
allowing the selection of one surrogate marker correlated to overall survival.
Presenting Author: Nathalie Lassau, Institut Gustave Roussy, Villejuif,
France
Background: A prospective study of dynamic contrast-enhanced ultrasound
(DCE-US) with quantification for the evaluation of antiangiogenic treatments
was launched (19 centers), supported by the French National
Cancer Institute. The objectives were the diffusion of the standardized
method, a cost evaluation and the identification of perfusion parameters
predicting tumor response. Methods: All patients had DCE-US at baseline,
D7, D14, D30, D60 and every two months. Each examination included a
bolus injection of sonovue (Bracco) and 3 minutes of raw linear data with an
Aplio (Toshiba). Raw data were analyzed with a mathematical model
(patent PCT/IB2006/003742) to evaluate 7 parameters characterizing the
tumor perfusion curve. Response to treatment was evaluated every 2
months with RECIST criteria. In order to have sufficient follow-up data, the
statistical analysis has to be performed more than 6 months after the
inclusion of the last analyzed patient. Inclusions were closed in March
2010. Results: A total of 539 patients have been included (mainly RCC
(157) and HCC (107)); more than 2 000 DCE-US and 1700 CT-scan were
performed. A follow-up more than 12 months showed that 3 parameters
have a strong significant difference (p�0.0003) according to the response
at 6 months. The decrease of more than 40% of AUC at one month is
correlated to the TTP (p� 001) and OS (p� 0.04). Conclusions: Final
results confirm the usefulness of this tool to monitor anti-angiogenic
treatments. The criteria: the decrease of more than 40% of AUC at one
month is predictive of response.
4620 General Poster Session (Board #7C), Sun, 8:00 AM-12:00 PM
Prospective exploratory analysis of the association between genetic polymorphisms
and sunitinib toxicity and efficacy in metastatic renal-cell carcinoma.
Presenting Author: Carlos Alberto Farfan, Hospital Universitario 12
de Octubre, Madrid, Spain
Background: Sunitinib (SU) is a multi-targeted receptor tyrosine kinase
inhibitor treatment that is approved for metastatic renal cell carcinoma
(mRCC). However, several patients either do not respond to treatment or
they experience significant toxicity.Our study aims to find genetic markers
of toxicity and efficacy using a commercially available DNA microarray
genotyping system. Methods: 30 patients with newly diagnosed mRCC,
from January 2010 to May 2011, were evaluated prospectively at Hospital
12 de Octubre (Madrid, Spain). Pts received SU 50 mg/day, 4 wks on / 2
wks off treatment schedule. A total of 92 of single nucleotide polymorphisms
(SNPs) in 34 genes in the pharmacokinetic and pharmacodynamic
pathways of drugs were analyzed using Drug inCode pharmacogenetic
service. SNPs in candidate genes, together with clinical characteristics
were tested univariately for association with the number of days of SU
treatment until the first reduction of dose, PFS and OS. Results: Complete
analysis was possible in 25 pts. Pts with CYP1A2*1/*1.a low metabolizing
genotype, had an increased risk of dose reductions due to toxicity compare
to allele *1F (Median time to dose reduction : 2.33 months vs NR;
p�0.006). Pts with CYP2C19*1/*1 , wild type genotype, had an increased
risk of dose reductions due to toxicity vs. other genotypes (Median time to
dose reduction: 2.8 vs 9.73 months; p�0.021). Catechol-O-methyltransferase
(COMT) V158M polymorphisms, was associated with PFS and OS
(Met/Met carriers median PFS and OS NR; Met/Val pts PFS� 15 months;
OS�17.2 months and Val/Val pts PFS�3.3 months; OS� 4.4 months ;
p�0.005 for PFS and p�0.003 for OS). Conclusions: This preliminary
analysis suggests that CYP1A2 and CYP2C19 SNPs may be associated with
toxicity in patients with RCC treated with SU. As CYP1A2 and CYP2C19
activity could be affected by a variety of non-genetic factors, if these is
confirmed, it could lead to the necessity of controlling toxic and dietary
habits of pts treated with SU. SNPs associated with toxicity and survival in
this preliminary analysis are being validated in an independent cohort of
RCC treated with SU (García-Donas J, et al. Lancet Oncol 2011).
4619 General Poster Session (Board #7B), Sun, 8:00 AM-12:00 PM
Use of bisphosphonates (Bis) combined with sunitinib (Su) to improve the
response rate (RR), progression-free survival (PFS), and overall survival
(OS) of patients (pts) with bone metastases (mets) from renal cell
carcinoma (RCC). Presenting Author: Avivit Peer, Rambam Health Care
Campus, Haifa, Israel
Background: Bis are used to prevent skeletal events of bone mets, and may
exhibit anti tumor effects. We aimed to evaluate whether Bis can bring a
RR, PFS, and OS benefit to pts with bone mets from RCC that are treated
with Su. Methods: We performed an international multicenter retrospective
study of pts with bone mets from RCC who were treated with Su. Pts were
divided into Bis users (group 1) and nonusers (group 2). The effect of Bis on
RR, PFS and OS, was tested with adjustment for known prognostic factors
using a chisquare test from contingency table and partial likelihood test
from Cox regression model. Results: Between 2004-2011, 244 pts with
metastatic RCC were treated with Su. 92 pts had bone mets, 41 group 1
and 51 group 2. The groups were balanced regarding the following known
prognostic factors: past nephrectomy, clear cell vs non clear cell histology,
initial diagnosis to sunitinib treatment (tx) time, presence of � 2 mets
sites, presence of lung/liver mets, ECOG performance status, anemia,
calcium level � 10 mg/dL, elevated alkaline phosphatase (AP), pre-tx
neutrophil to lymphocyte ratio (NLR) �3, sunitinib induced HTN, and the
use of angiotensin system inhibitors. They were also balanced with regard
to past cytokines/targeted tx, and mean sunitinib dose/cycle. Objective
response was partial response/stable disease 85% (n�35) vs 71% (n�36),
and progressive disease 15% (n�6) vs 29% (n�15) (OR 3.287, p�0.07)
in group 1 vs 2 respectively. Median PFS was 15 vs 5 months (HR 0.433,
p�0.035), and median OS not reached with a median folloup time of 43
mos vs 12 months (HR 0.398, p�0.003), in favor of group 1. In
multivariate analysis of the entire pt cohort (n�92), factors associated with
PFS were Bis use (HR 0.433, p�0.035), pre-tx NLR �3 (HR 0.405,
p�0.016), and elevated AP (HR�3.63, p�0.012). Factors associated
with OS were Bis use (HR 0.32, p�0.003), elevated AP (HR 3.18,
p�0.002), and Su induced HTN (HR 0.193, p� 0.001). Conclusions: Bis
may improve the outcome of Su tx in RCC with bone mets. This should be
investigated prospectively, and if validated applied in clinical practice and
clinical trials.
4621 General Poster Session (Board #7D), Sun, 8:00 AM-12:00 PM
Prognostic role of body composition parameters in renal cell carcinoma
(RCC). Presenting Author: Emilie Lanoy, Biostatistics and Epidemiology
Unit, Institut Gustave Roussy, Villejuif, France
Background: Previous studies have shown that body component i.e. muscle
tissue (MT) and adipose tissue (AT) are linked to overall survival (OS) and
progression free survival (PFS). The aim of our study is to analyze whether
MT and AT have a prognostic role in metastatic RCC treated with targeted
therapy. Methods: We investigated body mass index (BMI), MT and AT in
RCC pts. Analysis of CT image was used to evaluate cross-sectional areas
(cm2 ) of total AT (TAT), MT, and the grey level image (GLI) of MT, reflecting
physical properties of the scanned tissue and used as a proxy to describe
the quality of muscle. The 3rd lumbar vertebra (L3) was chosen as a
landmark since L3 and whole-body measurements are linearly related.
Images were analyzed using Slice-O-Matic software V4.3 (Tomovision).
Indexed on height MT (cm2 /m2 ), indexed on height TAT (cm2 /m2 ) and
mean GLI of MT were computed and described stratified on sex. For each
measurement, population was divided in two groups: patients with values �
or �� median observed in patient of the same gender and OS and PFS were
estimated using Kaplan-Meier method and compared with the log-rank
test. Multivariable Cox proportional hazards model were adjusted for
modified MSKCC risk group and treatment (active versus placebo). Results:
There were 113 men aged of 60 (interquartile range�52-56) years with
BMI of 26 (24-29) kg2 /m2 and 36 women aged of 58 (54-65) years with
BMI of 23 (20-26) kg2 /m2 . After adjustment for MSKCC (OS and PFS) and
active treatment (PFS), GLI of MT over the median was associated with
longer OS (HR�1.85, 95%CI�[1.22;2.82], p�.004) and PFS (HR�1.81,
95%CI�[1.22;2.65], p�.002) Conclusions: Quality of muscular tissue is
independently associated with better outcome in RCC. Surprisingly, adipose
tissue as well as BMI is not associated with survival in this study.
OS in months PFS in months
Label
Median P25 P75 p Median P25 P75 p
Indexed MT>� 14 cm 2 /m 2 (men)
or 13 cm 2 /m 2 24 14 49 .1213 6 4 13 .3128
(women)
Indexed MT< 14 cm 2 /m 2 (men)
or 13 cm 2 /m 2 19 10 39 5 3 9
(women)
Mean GLI >� 38 (men) or 36 (women) 29 18 62 .0011 8 4 15 .0007
Mean GLI < 38 (men) or 36 (women) 14 7 30 4 3 8
Indexed TAT >�326 cm 2 /m 2 (men)
or 231 cm 2 /m 2 24 14 45 .1725 6 4 11 .6124
(women)
Indexed TAT