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

3524 Poster Discussion Session (Board #16), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Randomized phase III study of adjuvant chemotherapy with oral uracil and
tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in
patients (pts) with stage III colon cancer (CC): Final results of Japan
Clinical Oncology Group study (JCOG0205). Presenting Author: Yasuhiro
Shimada, National Cancer Center Hospital, Tokyo, Japan
Background: NSABP C-06 reported the non-inferiority of oral adjuvant
uracil and tegafur plus leucovorin (UFT/LV) to weekly fluorouracil and
folinate (5-FU/LV) in disease-free survival (DFS) in stage II/III CC. Although
adjuvant FOLFOX for stage III is standard care in US or EU, its toxicity and
cost is major problem. This is the first report of JCOG0205, which
compared UFT/LV to standard 5-FU/levofoloinate (l-LV) in stage III CC.
Methods: Pts were randomized to 3 courses of 5-FU/l-LV (5-FU 500 mg/m2 ,
l-LV 250 mg/m2 , on days 1, 8, 15, 22, 29, 36, q8w), or 5 courses of
UFT/LV (UFT 300 mg/m2 /day, LV 75 mg/day, on days 1–28, q5w). Primary
endpoint was DFS. Sample size was 1,100, determined with one-sided
alpha of 0.05, power of 0.78, and non-inferiority margin of hazard ratio
(HR) of 1.27. Owing to interim analyses, the multiplicity-adjusted alpha
and confidence coefficient of CI in the final analysis were 0.0433 and
91.3%. Results: Between Feb 2003 and Nov 2006, 1,101 pts (1,092
eligible) were randomized to 5-FU/l-LV (n�550) or UFT/LV (n�551).
Median follow-up was 72.0 months, median age: 61, colon/rectum:
67%/33%, number of positive nodes �3/4�: 73%/27%, stage IIIa/IIIb:
75%/25%. The HR of DFS was 1.02 (91.3% CI, 0.84–1.23) and
non-inferiority of UFT/LV was demonstrated (P�0.0236). Incidences of
G3/4 toxicities were 8.4% neutropenia in 5-FU/l-LV and 8.7% ALT
elevation in UFT/LV. In the 2 arms (5-FU/l-LV, UFT/LV), diarrhea (9.6%,
8.5%) and anorexia (4.0%, 3.7%) were similar. G3/4 diarrhea was
one-third less and G3/4 ALT elevation was three times more common than
those in C-06. No treatment-related death was reported. Conclusions:
Adjuvant UFT/LV is demonstrated to be non-inferior to standard 5-FU/l-LV
in DFS. Five-year OS (87.5%) is favorable to 69.6% in C-06, possibly due
to D3 dissection and stage migration. UFT/LV should be an oral treatment
option for stage III CC.
5-FU/l-LV UFT/LV Overall
N 546 546 1,092
3Y DFS (%) 79.3 77.8 78.6
5Y DFS (%) 74.3 73.6 73.9
5Y OS (%) 88.4 87.5 87.9
N 544 540 1,084
G3/4 neutropenia (%) 8.4 1.5 5.0
G3/4 ALT (%) 0.7 8.7 4.7
G3/4 diarrhea (%) 9.6 8.5 9.0
3526 Poster Discussion Session (Board #18), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Smoking status and prognosis in patients with stage III colon cancer: A
correlative analysis of NCCTG phase III trial N0147. Presenting Author:
Amanda I. Phipps, Fred Hutchinson Cancer Research Center, Seattle, WA
Background: Prior observational studies have suggested that smoking is
associated with poorer overall survival after colon cancer (CC) diagnosis.
Using data from N0147, a phase III randomized adjuvant trial of patients
with stage III CC, we assessed the relationship between smoking status and
cancer outcomes (disease-free survival (DFS) and time to recurrence
(TTR)), accounting for possible heterogeneity by patient and tumor characteristics.
Methods: Patients completed a risk factor questionnaire at
baseline prior to randomization to FOLFOX or FOLFOX�cetuximab
(N�1968). Information was collected on smoking and other lifestyle
factors, including alcohol consumption, body mass index (BMI), and
physical activity. Multivariate Cox models assessed the association between
smoking history and the primary trial outcome of DFS, as well TTR,
adjusting for other lifestyle and clinical factors. The median follow-up was
3.5 years. Results: Overall, 52% of patients were former or current smokers.
Compared to never smokers, ever smokers experienced significantly shorter
DFS [3-year DFS: 70% vs 74%, hazard ratio (HR)�1.21, 95% confidence
interval (CI): 1.02-1.42]. This association persisted after adjusting for age,
sex, tumor subsite, number of nodes involved, T-stage, mismatch repair
deficiency, BRAF mutation status, performance score, physical activity,
BMI, and alcohol consumption (HR�1.23, 95% CI: 1.02-1.49). There was
significant interaction in this association by BRAF mutation status (p�0.02):
smoking was associated with shorter DFS in BRAF wildtype CC patients
(HR�1.25, 95% CI: 1.04-1.51) but not in BRAF mutant CC patients
(HR�0.72, 95% CI: 0.47-1.10). Patterns of association with smoking,
overall and by BRAF status, were identical in analyses of TTR. Conclusions:
Overall, smoking was significantly associated with shorter DFS and TTR in
CC patients. These adverse relationships were most evident in patients with
BRAF wildtype CC.
Gastrointestinal (Colorectal) Cancer
3525 Poster Discussion Session (Board #17), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Comparative evaluation of capecitabine or infusional leucovorin/5-fluorouracil
(LV/5-FU) with or without oxaliplatin (Ox) for stage III colon cancer (CC): A
pooled analysis of individual patient data from four randomized controlled trials.
Presenting Author: Weijing Sun, Abramson Cancer Center at the University of
Pennsylvania, Philadelphia, PA
Background: A fluoropyrimidine � Ox is the standard of care for stage III CC but a
fluoropyrimidine alone is recommended for selected patients in several practice
guidelines. We assessed efficacy and safety of adjuvant capecitabine � Ox vs.
LV/5-FU � Ox across a population of stage III CC patients enrolled in four trials.
Methods: N � 5,819 patients from NSABP C-08, XELOXA, X-ACT, and AVANT
were pooled and analyzed; bevacizumab-treated patients were excluded. Endpoints
were disease-free survival (DFS, primary), relapse-free survival (RFS),
overall survival (OS), and safety. Multivariate Cox regression analyses (MVA)
controlled for age, gender, T, and N stage. Results: Patient demographics and
disease characteristics (except lymph nodes examined) were well balanced
across groups. The number of patients receiving capecitabine and LV/5-FU were
1,942 and 3,877, respectively. Median follow-up was shorter in NSABP C-08
and AVANT (36 and 50 months) vs. XELOXA and X-ACT (83 and 74 months).
Five-year DFS was 62.8% for capecitabine � Ox and LV/5-FU � Ox. The
capecitabine by Ox interaction was significant for OS with a trend for DFS and
RFS; likely due to improved outcomes with capecitabine alone and similar
outcomes for capecitabine or LV/5-FU � Ox. Serious adverse event (AE) rates
were similar for LV/5-FU- and capecitabine-based therapy (16% vs. 20%,
respectively). Overall, treatment-related grade 3/4 AEs were more common with
LV/5-FU (59% vs. 47%). Treatment-related grade 3/4 AEs of interest included
peripheral sensory neuropathy (5% vs. � 1%), diarrhea (12% vs. 15%), febrile
neutropenia (2% vs. � 1%), and hand–foot syndrome (� 1% vs. 12%).
Conclusions: Adjuvant capecitabine � Ox and LV/5-FU � Ox show comparableefficacy
benefits for the treatment of stage III CC; further supporting capecitabine
or LV/5-FU-based regimens as standard options for the adjuvant therapy of stage
III CC.
Capecitabine � Ox vs.
LV/5-FU � Ox
Univariate MVA
Cox regression HR
95% CI P
209s
Ox interaction HR
95% CI P
DFS 1.01 .86 1.14 .17
0.92–1.10 0.95–1.37
RFS 1.01 .86 1.15 .15
0.92–1.11 0.95–1.39
OS 1.02 .65 1.33 .01
0.92–1.14 1.06–1.67
3527 Poster Discussion Session (Board #19), Fri, 1:00 PM-5:00 PM and
4:30 PM-5:30 PM
Adjuvant chemotherapy (AC) use and outcomes in stage II colon cancer
(CC) with and without poor prognostic features. Presenting Author: Aalok
Kumar, British Columbia Cancer Agency, Vancouver, BC, Canada
Background: AC is frequently considered inpatients (pts) with �high risk�
stage II CC, defined by the presence of �/�1 poor prognostic features, such
as obstruction or perforation, T4 stage, �12 lymph nodes retrieved,
positive margins, and lymphovascular or perineural invasion. However,
survival benefits associated with AC use in high risk pts remain largely
unproven. Our aims were to 1) examine patterns of AC use in stage II CC
and 2) explore the relationship between AC use and survival in high vs low
risk pts. Methods: All pts diagnosed with stage II CC in British Columbia
from 1999 to 2008 and evaluated at any 1 of 5 regional centers were
reviewed. Kaplan-Meier and Cox regression methods were used to correlate
a) high vs low risk status and b) receipt of AC with relapse-free (RFS),
disease specific (DSS) and overall survival (OS). Results: We identified
1,697 stage II CC pts: 1,236 (73%) high risk and 461 (27%) low risk
among whom 363 (29%) and 61 (13%) received AC, respectively.
Individuals with high risk features who received AC were younger (median
62 vs 72 years, p�0.001) and had better performance status (ECOG 0/1
47% vs 34%%, p�0.02). In the high risk group, AC was associated with
improved 5-year OS, but not with RFS or DSS (Table). After adjusting for
confounders, an OS advantage from AC persisted for high risk pts (HR
0.67, 95CI 0.52-0.86, p�0.002), but no significant RFS or DSS benefits
were seen (HR 0.76, 95CI 0.58-0.99, p�0.05 and HR 0.75, 95CI
0.55-1.02, p�0.11, respectively). Subgroup analyses showed that individuals
with T4 lesions had improved RFS (HR 0.63, 95CI 0.42-0.95,
p�0.03), DSS (HR 0.59, 95CI 0.37-0.93, p�0.02), and OS (HR 0.50,
95CI 0.33-0.77, p�0.002). Conclusions: In this population-based cohort
of stage II CC, AC was associated with an OS advantage in high risk pts,
likely due to pt selection. RFS and DSS benefits were mainly seen in T4
lesions, suggesting a limited role for AC in pts deemed high risk based on
clinical and pathological factors. Risk stratification based on molecular
testing should be further explored.
Survival in high vs low risk stage II CC.
3-year RFS % p value 5-year DSS % p value 5-year OS % p value
High risk
AC 78 0.98 80 0.83 75 �0.01
No AC 80 79 68
Low risk
AC 87 0.18 93 0.78 87 0.26
No AC 93 93 85
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