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

3565 General Poster Session (Board #28C), Mon, 8:00 AM-12:00 PM
Bevacizumab (BEV) plus capecitabine as maintenance therapy after initial
treatment with BEV plus XELOX in previously untreated patients (pts) with
metastatic colorectal cancer (mCRC): Mature data from STOP and GO, a
phase III, randomized, multicenter study. Presenting Author: Suayib
Yalcin, Hacettepe University Medicine Faculty, Ankara, Turkey
Background: Colorectal cancer is one of the most frequent malignancies,
second after breast cancer in women and third after lung cancer and
prostate cancer in men. The aim of this study was to evaluate and compare
the progression-free survival (PFS) between two arms: Arm A is a combination
of BEV � XELOX; Arm B is a combination of BEV � XELOX for 6 cycles
followed by maintenance BEV � capecitabine as first-line therapy in
mCRC. Methods: BEV (7.5 mg/kg) � XELOX (capecitabine 1000 mg/m2 bid
d1–14 � oxaliplatin 130 mg/m2 d1 q3w) were administered until progression
(Arm A) or 6 cycles of BEV � XELOX followed by BEV � capecitabine
were administered until progression (Arm B). PFS was the primary
endpoint; secondary endpoints included overall survival (OS), objective
response rate (ORR), and safety. A sample size of 118 pts was required to
detect with 80% power an increase of 1.5 months in median PFS between
two arms with a standard deviation of 3.9 months and significance level of
0.05 (10% drop-out rate). Results: A total of 123 pts were randomized.
Demographic characteristics were balanced between the arms. Median
treatment period was 7.5 (range 0.5–13.9) and 8.1 (range 0.1–20.7)
months in Arms A and B, respectively. There was a statistically significant
difference in median PFS between arms, although there was no significant
difference in ORR and OS (see table). Tolerability was acceptable in both
arms with the following grade 3/4 adverse events (AEs): Arm A 48.4%; Arm
B 34.4% (p�0.116). Grade 3/4 diarrhoea occurred in 9.7% vs. 3.3%,
weakness in 8.1% vs. 8.2%, hand-foot syndrome in 3.2% vs. 1.6%, and
neuropathy in 4.8% vs. 3.3% of pts in Arms A and B, respectively.
Conclusions: These findings suggest that maintenance therapy with BEV �
capecitabine following induction with 6 cycles of BEV � XELOX may be
superior to continuous BEV � XELOX until progression inpts with previously
untreated mCRC.
Arm A
(n�62)
Arm B
(n�61) p value
Efficacy
Median PFS, months
8.3
11.0
0.002
(95% CI)
(7.1–9.5) (9.1–12.9)
Median OS, months 20.2 23.8 0.1
ORR, % 58.9 66.7 0.861
3567 General Poster Session (Board #29B), Mon, 8:00 AM-12:00 PM
Implications of generating genetic test results for colon cancer in the
international, population-based colon cancer family registry. Presenting
Author: Louise A. Keogh, The University of Melbourne, Melbourne, Australia
Background: The ability to genotype large numbers of people rapidly and
inexpensively for research purposes highlights the need to develop guidelines
for providing medically-relevant research results - including unanticipated
findings - to study participants. The Colon Cancer Family Registry
(C-CFR) is the oldest and largest international colon cancer populationbased
registry; its experience managing genetic research findings can offer
guidance to clinicians and researchers. The C-CFR has enrolled 10,019
cases with colon cancer and 24,708 family members in six registries in the
US, Canada, Australia, and New Zealand. Deleterious (“high risk”) germline
mutations have been identified in DNA mismatch repair (MMR) genes
(MLH1, MSH2, MSH6, PMS2) and the MutYH gene. The aims of this
presentation are to: (1) report the uptake of genetic test results by C-CFR
participants; (2) systematically compare disclosure protocols and barriers
to uptake by registry; (3) make recommendations to guide clinicians and
researchers. Methods: Uptake of genetic test results was calculated from
data collected by the C-CFR; key investigators (KIs) from each registry
completed a survey about disclosure decision-making; KIs also took part in
discussions to generate recommendations. Results: Registry-wide molecular
testing has identified deleterious MMR germline mutations for at least
one member of 424 families (4%) and 48 biallelic MutYH gene carriers.
Uptake of test results ranged from 56-86% (n� 1542) across registries.
Barriers to disclosure include: (1) lack of pre-existing notification protocols;
(2) logistics of re-consent; (3) limited involvement of genetic
counselors at some registries; (4) in the US, the requirement that genetic
testing be performed in a CLIA approved laboratory; (5) IRBs declining
approval; and (6) budget constraints. Conclusions: Based on our international
registry’s findings we recommend that researchers generating genetic
information establish plans for disclosure at the outset; obtain
subject consent a priori; consider subject knowledge and disclosure
preferences; provide guidance and budget for clinical follow-up; and
involve genetic counselors.
Gastrointestinal (Colorectal) Cancer
219s
3566 General Poster Session (Board #29A), Mon, 8:00 AM-12:00 PM
Prognostic significance of lymph node retrieval in localized rectal cancer
(RC): A registry analysis of 8,964 patients (pts). Presenting Author:
Amandeep Gill, University of California, Davis, Sacramento, CA
Background: In contrast to colon cancer, the prognostic implications of
reduced lymph node retrieval in RC are unclear. We investigated the
association between the total number of lymph nodes examined in early
stage RC and disease specific survival (DSS) in two cohorts: 1) pts who
underwent surgery and adjuvant (ADJ) chemoradiation (chemoXRT), and 2)
those who received neoadjuvant (NEO) chemoXRT. Methods: Using the
California Cancer Registry, we identified 8,946 pts with stage I – III RC
diagnosed from 2000 to 2007. Of these, 4,790 underwent tri-modality
therapy: 2,946 patients (61.5%) had NEO chemoXRT and 1,844 patients
(38.5%) had ADJ chemoXRT. Multivariate Cox proportional hazards models
were constructed for DSS, adjusting for age, sex, race, socioeconomic
status, T-stage and lymph node number. DSS was compared between NEO
and ADJ cohorts within separate subgroups of pathologic node positive and
node negative RC. Results: Although there was no difference in overall DSS
between the NEO and ADJ cohorts, the median number of lymph nodes
examined was reduced in patients who had undergone NEO chemoXRT (8
vs. 11, p�0.0001). For all pts treated with tri-modality therapy, advancing
age and higher T-stage were associated with significantly reduced DSS.
Positive lymph nodes were associated with worse DSS regardless of the
timing of therapy, although the effect was stronger for residual lymph nodes
in the NEO cohort (HR 2.8 vs. 1.8 in ADJ cohort, p�0.001). For node
negative pts in the ADJ cohort, increased lymph node retrieval was
associated with improved DSS (HR per node 0.952, p�0.017); however,
no association between lymph nodes examined and DSS was seen in the
NEO cohort (p�0.282). Conclusions: Residual positive lymph nodes in pts
treated with NEO chemoXRT are more strongly associated with poorer DSS
than in pts treated with surgery and ADJ chemoXRT. NEO chemoXRT
dissociates the connection between lymph node retrieval and survival in
RC. This finding highlights a key difference between colon and RC and
underscores the need for a different interpretation of the pathologic
findings after NEO therapy.
3568 General Poster Session (Board #29C), Mon, 8:00 AM-12:00 PM
Association of microsatellite instability with prognosis in the pathologic N2
colon cancer patients treated with adjuvant FOLFOX chemotherapy. Presenting
Author: Jeong Eun Kim, Asan Medical Center, Seoul, South Korea
Background: The impact of microsatellite instability (MSI) on survival has
been rarely explored, with controversy, in stage III colon cancer treated with
adjuvant 5-flurouracil-oxaliplatin combination (FOLFOX) chemotherapy.
We evaluated association between MSI and survival in this population.
Methods: We analyzed 312 patients (pts) with curatively resected stage III
colon cancer treated with adjuvant FOLFOX chemotherapy. We determined
MSI status using polymerase chain reaction amplification as high levels of
MSI (MSI-H, � 2 unstable markers), low levels of MSI (MSI-L, 1 unstable
marker), and microsatellite stable (MSS, no unstable marker). Results: Of
312 pts, 8.3% showed MSI-H and they were younger (median age, 51.5 vs.
58 years, p�0.018). MSI-H tumors were more commonly located ascending
colon (46.2% vs. 23.1%, p�0.002) and had poorly differentiated
features (30.8% vs. 5.2%, p�0.0001). After the median follow-up of 30.9
months, 3-year relapse-free (RFS) and overall survival (OS) rates were
76.1% and 91.7%, respectively. In univariate analysis, pathologic N2
(pN2) was associated with reduced RFS (p�0.0001) and OS (p�0.002),
while MSI status did not affect either RFS (p�0.254) or OS (p�0.961). In
patients with pN2 tumors, however, MSI-H was associated with better
survival compared with MSS/MSI-L; the RFS and OS in pts with pN2/MSI-H
were comparable to those in pts with pN1 tumors (table). Conclusions: MSI
status alone did not affect survival in our population. However, pts with
pN2/MSI-H showed favorable survival outcomes comparable to those with
pN1, and MSS/MSI-L/pN2 was associated with worst survival, implicating
that MSI-H modifies the inherent worse prognosis of pN2 tumors.
pN1 pN2
MSS/MSI-L MSI-H MSS/MSI-L MSI-H p value
3yr RFS (%) 86.4 88.0 58.9 85.7 �0.0001
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