In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 4605-4605
Abstract:
4605 Background: The identification of molecular prognostic and/or predictive determinants of outcome in pts with mRCC is an important challenge. We hypothesized that specific tumor DNA copy number alterations (CNAs) - loss of chr 14 or 14q (14/14q-), and gain of chr 5q (5q+) may predict likelihood of pazopanib treatment benefit in pts with mRCC. Methods: Pts DNA samples from the Phase II (VEG102616) pazopanib trial were analyzed by using Affymetrix OncoScan. Copy no. data were moving smoothed and normalized. The copy no. and allele difference were profiled according to their chromosome locations to interrogate CNA and LOH. Objective response (OR, RECIST) and progression free survival (PFS) were determined by investigators (IN) and an independent review (IR) committee. OR and PFS data were analyzed using exact and Kaplan-Meier tests. Results: Tumor DNA samples from 75 pts were adequate for CNA analysis. 14/14q- was found in 35/75 pts (46.7%), and 5q+ was found in 37/75 (49.3%). 14/14q- was present in the tumors of 12/31 pts (39%) with OR by IR compared with 23/44 (52%) nonresponding pts (p=0.347). 14/14q- did not affect PFS. 5q+ was present in tumors of 17/31 pts (55%) with OR and 20/44 (45%) nonresponding pts (p=0.486). PFS was longer in pts with 5q+ tumors compared with those without 5q+ (log rank p=0.026), with median PFS of 66 vs 35 wks, respectively. The odds of achieving OR decreased as the total number of chromosomal gains/losses increased (p=0.032, odds ratio 0.49), but this had no effect on PFS. In exploratory analysis, we examined the combined effect of both 14/14q- and 5q+ on PFS (Table). Conclusions: Pts with 5q+ tumors have significantly longer PFS, with no effect on OR rate. While 14/14q- alone had no effect on outcomes, the combination of 5q+ and no 14/14q- was associated with significantly greater PFS. Pts with more genetically complex tumors were less likely to obtain OR with pazopanib. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.4605
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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