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treatment at week 4, and week 12 by using Searchlight Protein Array (Aushon). CAF
levels at each time point and changes of CAF levels from baseline at week 4 and
week 12 were correlated with maximum tumor shrinkage (MTS) by linear regression;
PFS by Cox regression; baseline tumor burden using baseline sum of longest tumor
diameter and best response by Spearman.
Results: Decreases in OPN levels from baseline at week 4 (p = 0.030) and week 12
(p = 0.006) show significant correlations with MTS. At week 4, changes in E-Selectin
from baseline was trending (p = 0.053) in correlation with MTS. With PFS, changes
in IL-6 level from baseline at week 12 has near significant correlation with PFS (p =
0.05). E-Selectin has an inverse baseline to week 4 significant correlation with best
response status week 4 (p = 0.0245) but not at week 12.
Conclusion: Decreasing levels of osteopontin from baseline at week 4 and 12
correlated with improved tumor shrinkage; while increase in IL-6 portends shorter
PFS and E-Selectin was inversely correlated with best response status. Additional
investigation is needed to evaluate the dynamic changes of CAFs as an approach to
monitor patients while on pazopanib therapy as marker of tumor response.
Disclosure: Y. Liu: Stock ownership: Yes; GSK Membership on an advisory board or
board of directors: No Corporate-sponsored research: No Other substantive
relationships: NoA. Martin: Stock ownership: Yes; GSK Membership on an advisory
board or board of directors: No Corporate-sponsored research: No Other substantive
relationships: NoK.L. Baker-Neblett: Stock ownership: Yes; GSK Membership on an
advisory board or board of directors: No Corporate-sponsored research: No Other
substantive relationships: No. L.N. Pandite: Stock ownership: Yes; GSK Membership
on an advisory board or board of directors: No Corporate-sponsored research: No
Other substantive relationships: No. J.V. Heymach: Stock ownership: No Membership
on an advisory board or board of directors: Yes; GSK Corporate-sponsored research:
Yes; GSK for biomarker analysis. Other substantive relationships: No. All other
authors have declared no conflicts of interest.
834P RECIST RESPONSE OF THE PRIMARY LESION IN
METASTATIC RENAL CELL CARCINOMAS TREATED WITH
SUNITINIB: DOES THE PRIMARY LESION HAVE TO BE
REGARDED AS A TARGET LESION?
I. Park 1 , K. Park 1 , S. Park 1 ,Y.Ahn 1 , J. Ahn 1 , H.J. Choi 2 , C. Song 3 , H. Ahn 3 ,
J.H. Hong 3 , J. Lee 1
1 Department of Oncology, Asan Medical Center, University of Ulsan College of
Medicine, Seoul, KOREA, 2 Department of Radiology, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, KOREA, 3 Department of Urology,
Asan Medical Center, University of Ulsan College of Medicine, Seoul, KOREA
Background: There is no consensus on including the primary lesion as the target
lesion when evaluating the response of non-nephrectomized metastatic renal cell
carcinoma (mRCC) patients (pts). We evaluated whether best overall response
changes by designating primary renal lesions as either target or non-target lesions
and assessing response per RECIST in mRCC pts treated with sunitinib. In addition,
we evaluated whether discordance, if any, leads to a difference in predictive value of
response in terms of time-to-progression (TTP) and overall survival (OS).
Patients and methods: Among pts with histologically confirmed mRCC treated with
sunitinib at Asan Medical Center, pts with an intact primary tumor and at least one
extra-renal measurable lesion were included. To measure the influence of including
the primary lesion as the target lesion, the variation of the sum of diameters (ΔSOD)
of target lesions and best overall response, assessed from all target lesions and from
metastasis-only target lesions, was documented separately. For examining differences
of two methods in predictive function in estimating TTP and OS, pts were
categorized according to their best overall responses as responders [complete
response (CR) and partial response (PR)] or non-responders [stable disease (SD) and
progressive disease (PD)] for all target lesions and metastasis-only target lesions,
respectively, and then analyzed for survival.
Results: Forty-one pts were included in this study. Median ΔSOD of the primary
lesion and metastatic target lesion were −6.0% (range, −34.0–17.6%), and −18.0%
(range, −100.0–120.0%), respectively. For metastasis-only target lesions, the best
overall response of two pts (4.9%) changed from SD to PR. When we categorized pts
into responders and non-responders, response determination using metastasis-only
target lesions resulted in significantly better discrimination of TTP (14.9 vs 4.3
months, P = 0.001) and OS (18.5 vs 9.6 months, P = 0.036) between two groups.
Using all target lesions, both TTP (14.9 vs 5.4 months, P = 0.056) and OS (18.0 vs
10.6 months, P = 0.155) were not statistically significant.
Conclusion: When treating non-nephrectomized mRCC pts, selecting
metastasis-only lesions as target lesions might be better to determine response, which
might be more representative of TTP and OS.
Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
835P TISSUE MICROARRAY (TMA) AND VHL MUTATIONS AS
PREDICTORS OF OUTCOME IN ADVANCED CLEAR CELL
RENAL CELL CARCINOMA (CCRCC) TREATED WITH FIRS
LINE SUNITINIB
J.F. Rodríguez-Moreno 1 , E. Esteban 2 , M. Morente 3 , I. Alemany 4 ,
D.E. Castellano 5 , A. Gonzalez Del Alba 6 , M. Climent 7 ,
C. Rodriguez-Antona 3 , J. Garcia-Donas 1
1 Medical Oncology, Centro Integral Oncológico Clara Campal, Madrid, SPAIN,
2 Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, SPAIN,
3 Human Genetic, Spanish National Cancer Research Center, Madrid, SPAIN,
4 Medical Oncology, Hospital Universitario Fundacion Alcorcon, Alcorcon, SPAIN,
5 Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, SPAIN,
6 Medical Oncology, Hospital Universitario Son Espases, Palma de Mallorca,
SPAIN, 7 Medical Oncology, Instituto Valenciano de Oncologia, Valencia, SPAIN
Introduction: Sunitinib is a standard treatment for kidney cancer, however in some
patients response is lacking. Molecular predictors of outcome could deeply impact
patient care.
Methods: We conducted an observational, prospective study in 15 institutions
members of the Spanish Oncology Genitourinary Group (SOGUG). Inclusion criteria
were patients with confirmed advanced clear cell renal cell carcinoma with no prior
treatment, planned to receive sunitinib according to local practice.From paraffin
embedded tumor samples a Tissue MicroArray (TMA) was constructed and
evaluated independently by two pathologists, also blinded to clinical data. Expression
of Carbonic Anhydrase IX, P-glicoprotein, Vascular Endothelial Growth Factor
(VEGF), VEGF-Receptor 1,2 and 3 (VEGFR1,2 and 3), Platelet-Derived Growth
Factor Receptor (PDGFR-Beta), Hypoxia-Inducible Factor 2 alpha (HIF2α) and Von
Hippel-Lindau protein (pVHL) was assessed. In addition the presence of VHL gene
mutations was studied.
Results: 101 patients were recruited from 2007 to 2010. TMA was constructed from
69 tumor samples. In multivariable analysis, HIF2α (HR 0.17 (0.05-0.64) p = 0.0083)
and PDGFRβ (HR 0.042 (0.003-0.70) p = 0.028) overexpression correlated with
progressive disease (PD) as best response. A similar trend in PFS and OS was
observed for HIF-alfa but did not reach statistical significance.Progression free
survival (PFS) was longer in cases with high VEGFR3 expression (HR 0.42
(0.21-0.83) p = 0.013). Interestingly, low levels of this protein strongly correlated
(r = -0.441 P = 0.0003) with the presence of a germline SNP (VEGFR3 rs307826) that
has been previously identified as a sunitinib resistance predictor by our group.Finally
overexpression of VEGF (HR 4.6 (1.5-13.6), p= 0.0063), and VEGFR1 (HR 6.2
(1.2-32.2) p = 0.031) were associated with poor overall survival (OS).VHL gene
alterations could only be determined in 30 cases, with 20 (66%) presenting a
pathological mutation. No association with outcome could be established.
Conclusion: Expression of some proteins involved in neoangiogenesis pathway could
play a role in sunitinib sensitivity and resistance. A significant association between
low expression of VEGFR3 and one SNP in such gene, both correlated with poor
outcome, deserves further investigation.
Disclosure: All authors have declared no conflicts of interest.
836P PROGNOSTIC FACTORS AND VALIDATION OF PROGNOSTIC
NOMOGRAMS IN PATIENTS (PTS) TREATED WITH 3
TARGETED THERAPIES (TTS) FOR METASTATIC RENAL CELL
CARCINOMA (MRCC): RESULTS FROM AN ITALIAN SURVEY
R. Iacovelli 1 , M. Rizzo 2 , V. Lorusso 3 , F. Atzori 4 , P.A. Zucali 5 , C. Sacco 6 ,
F. Boccardo 7 , F. Valduga 8 , F. Massari 9 , G. Procopio 10
1 Department of Radiology, Oncology and Human Pathology, Sapienza University
of Rome, Rome, ITALY, 2 Medical Oncology, Azienda Ospedaliera Antonio
Cardarelli, Naples, ITALY, 3 Medical Oncology Unit, Ospedale Vito Fazzi, Lecce,
ITALY, 4 Medical Oncology, Azienda Ospedaliero Universitaria Cagliari,
Monserrato, ITALY, 5 Department of Oncology, Humanitas Cancer Center IRCCS,
Rozzano, ITALY, 6 Medical Oncology, University Hospital, Udine, ITALY, 7 Dept. of
Medical Oncology B, IRCCS AOU San Martino - IST-Istituto Nazionale per la
Ricerca sul Cancro, Genova, ITALY, 8 Medical Oncology, St Chiara Hospital,
Trento, ITALY, 9 Medical Oncology, Azienda Ospedaliera Universitaria Integrata
Verona-“Borgo Roma”, Verona, ITALY, 10 Medical Oncology, Fondazione IRCCS -
Istituto Nazionale dei Tumori, Milano, ITALY
Background: Outcomes of pts treated with three TTs for mRCC have not been well
characterized. Survival data as well as existing prognostic criteria in this population
were evaluated.
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