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

4622 General Poster Session (Board #7E), Sun, 8:00 AM-12:00 PM
Adherence to oral anticancer drugs (OAD) in patients (pts) with metastatic
renal cancer (mRCC): First results of the prospective observational multicenter
IPSOC study (Investigating Patient Satisfaction with Oral Anticancer
Treatment). Presenting Author: Pascal Wolter, Department of
General Medical Oncology, University Hospitals Leuven, Leuven, Belgium
Background: Patient adherence to oral therapy is a critical issue in cancer
treatment. The aim of this study is to investigate the prevalence and
severity of non-adherence to OAD in mRCC and to identify factors
predictive of non-adherence. Methods: Prospective observational multicenter
trial performed at 11 Belgian academic and non-academic centers.
All pts with mRCC starting OADs (sunitinib, pazopanib, everolimus or
sorafenib) are eligible for the study. Pts are contacted by phone at baseline
and at 1, 3, 6 and 12 months. At each contact, pts are asked to complete
questionnaires investigating 1) medication adherence (MMAS), 2) patient
satisfaction with treatment (CTSQ) and with treatment education (PS-
CaTE), 3) the extent of information desire (EID), 4) quality of life (FACT-G
and FKSI) and 5) the role of the pharmacist (SWiP). Adherence is measured
using an electronic medication event monitoring system (MEMS, Aardex).
Results: Between 02/2011 and 11/2011, 49 pts (m: 33, f: 16) with a
median age of 63 years (range 25 - 87) have participated in the IPSOC
study. Twenty-nine pts (64%) were treated with an OAD in first-line, 15 pts
(33%) in second-line. With a median follow-up of 131 days (range 2 - 313)
45 pts (92%) claimed to be fully adherent to their treatment (based on
MMAS and CTSQ data). Four patients indicated to have missed at least one
dose, of whom two indicated they occasionally forgot their medication and
two others interrupted treatment because of side effects. Based on MEMS
data, mean adherence, defined as the percentage of days with at least the
prescribed number of dosage taken, was 98.91%. Conclusions: The IPSOC
study, the first to examine adherence to OAD among mRCC pts, shows that
mRCC pts are almost fully adherent to treatment recommendations. This
seems to be in contrast to adherence data for other, long-lasting, anticancer
treatments. Further investigations will focus on the question
whether extensive counseling and participation in side-effect programs
contribute to the high percentage of adherence in this study.
4624 General Poster Session (Board #7G), Sun, 8:00 AM-12:00 PM
Molecular characterization of SETD2, a histone methyltransferase, in clear
cell renal cell carcinoma (ccRCC). Presenting Author: Thai Huu Ho,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Although the von Hippel-Lindau (VHL) tumor suppressor is
mutated in 60% of ccRCC, deletion of VHL in mice is insufficient for
tumorigenesis. Sequencing of ccRCC tumors identified mutations in
SETD2, a histone H3 lysine 36 (H3K36) trimethyltransferase. We hypothesize
that loss of SETD2 methyltransferase activity decreases H3K36
trimethylation (H3K36Me3) in ccRCC, and contributes to the cancer
phenotype. Methods: H3K36Me3 immunohistochemical (IHC) staining was
quantitated in wild-type and mutant SETD2 nephrectomy tissue. To
establish frequency of SETD2 loss of heterozygosity (LOH), genomic DNA
was isolated from 51 VHL deficient ccRCC specimens and analyzed with
Affymetrix single-nucleotide polymorphism (SNP) arrays. To evaluate
alterations of histone modifications in advanced ccRCC, H3K36Me3 IHC
was quantitated on tissue microarrays (TMAs) representing 28 paired
ccRCC specimens with unaffected kidney parenchyma and 40 metastases.
To identify kidney-specific H3K36Me3 binding sites, chromatin immunoprecipitation
(ChIP) sequencing was performed on nephrectomy specimens.
Results: Nephrectomy specimens with SETD2 truncating mutations
have decreased H3K36Me3 (�50%) compared to uninvolved kidney
tissue. Using SNP arrays, LOH at chromosome 3p (location of VHL and
SETD2 genes) was detected in �90% of the tested tumors. IHC reveals a
27.4% and 52.0% decrease in H3K36Me3 positive nuclei in primary
ccRCC and metastases, respectively, when compared to matched adjacent
unaffected kidney tissue (p �0.0001). Using ChIP sequencing, 421 and
1,718 genomic regions were upregulated in the tumor and unaffected
kidney tissue. Conclusions: SETD2 truncating mutations in patient-derived
tissue have decreased H3K36Me3 indicating that SETD2 is a nonredundant
H3K36 methyltransferase. LOH of VHL and SETD2 occurs in
�90% of tested ccRCC tumors. Genomic regions enriched for H3K36Me3
binding are being validated in additional patient-derived tissues. H3K36Me3
is decreased in primary ccRCC and even more in metastases, suggesting
that SETD2 methyltransferase activity is progressively misregulated in
RCC. Loss of SETD2 activity may cooperate with VHL silencing to promote
tumorigenesis.
Genitourinary Cancer
307s
4623 General Poster Session (Board #7F), Sun, 8:00 AM-12:00 PM
Trends in the use of cytoreductive nephrectomy for metastatic renal cell
carcinoma in the VEGFR tyrosine kinase inhibitor era. Presenting Author:
Che-Kai Tsao, Division of Hematology and Medical Oncology, The Tisch
Cancer Institute, Mount Sinai School of Medicine, New York, NY
Background: Two large randomized trials (SWOG, EORTC) published in
2001 established the role of cytoreductive nephrectomy (CyNx) for the
treatment of metastatic renal cell carcinoma (mRCC) in the cytokine era. A
paradigm shift occurred in 2005 with the approval of VEGFR tyrosine
kinase inhibitors (TKIs). We hypothesized that uncertainty regarding the
role of CyNx in the VEGFR TKI era has resulted in a change in practice
patterns. Methods: Using the Surveillance, Epidemiology and End Results
(SEER) registry, we identified 2780 patients with histologically-confirmed
mRCC between 2000 and 2008 who underwent CyNx or no surgery.
Patients were separated into pre- or VEGFR TKI-eras (2000-2005 vs.
2006-2008). Differences in baseline characteristics between these patient
groups were assessed and controlled for in a logistic regression analysis to
determine the likelihood of undergoing CyNx. Results: Overall, 1202 of
2780 patients (43%) underwent CyNx. CyNx increased from 41% in 2000
to 49% in 2005, and decreased to 35% in 2008, with a 20% decreased
likelihood of undergoing CyNx in the VEGFR TKI era compared to the
pre-VEGFR TKI era. Logistic regression analysis showed that tumor size,
age, race, marital status and pre- versus post-2005 periods were independent
predictors of CyNx (Table). Patients who were non-Caucasian, single,
with primary tumor �3cm, or older were less likely to undergo CyNx.
Conclusions: Use of CyNx increased after supporting level I evidence was
published in 2001, and decreased after regulatory approval of VEGFR TKIs
in 2005. Racial and demographic differences exist in the utilization of
CyNx. The results of pending randomized trials evaluating the role of CyNx
in the TKI-era are awaited to optimize use of this modality and address
potential disparities.
Logistic regression model for use of CyNx in 2000-2008.
Variable (reference) Odds ratio Std error p value
Post-2005 (Pre-2005) 0.802 0.092 0.0161
Primary tumor size >3cm (