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

3556 General Poster Session (Board #25C), Mon, 8:00 AM-12:00 PM
Exploratory analysis of adjuvant chemotherapy benefits after preoperative
chemoradiotherapy and radical resection for rectal cancer. Presenting
Author: George J. Chang, University of Texas M. D. Anderson Cancer
Center, Houston, TX
Background: Evidence regarding adjuvant chemotherapy (CTx) for patients
with rectal cancer after preoperative chemoradiotherapy (CXRT) is limited.
The aim of study was to explore the relationship between CXRT response
and adjuvant CTx for patients with rectal cancer treated by CXRT and
radical resection. Methods: We performed a retrospective consecutive
cohort study of patients with locally advanced (cStage II-III by EUS, CT, or
MRI) rectal carcinoma treated with preoperative CXRT and radical resection,
1993 to 2008. To explore the late effects, we performed a landmark
analysis of patients alive without recurrence at 24 months. The duration
free from recurrence (FFR) was compared among patients with complete
(CR, ypT0N0), intermediate (IR, ypT1-2N0), or poor (PR, ypT3-4 or N�)
response according to adjuvant CTx use and type using multivariate Cox
regression. Results: A total of 725 patients met criteria and were evaluated.
Median follow-up was 69 months (IQR: 39-104 months). 611 patients
received adjuvant CTx: 447 with fluoropyrimidine only (FP), and 139 also
received oxaliplatin (Ox). Although receipt of adjuvant chemotherapy was
not associated with 5-year FFR overall, (HR: 0.91, 95% CI: 0.58-1.43),
adjuvant therapy did appear to suggest a benefit in the IR group (HR, 0.49;
95%CI, 0.21-1.19). 2-year landmark analysis showed that adjuvant CTx
was associated with a significant improvement in FFR among the IR
patients only (HR, 0.28; 95% CI, 0.08-1.00, p�0.04). Among PR patients
FP alone did not improve FFR (HR, 1.22; 95% CI, 0.7-2.12) but the
addition of Ox was associated with a non-significant reversal in the
direction of the effect (HR, 0.53; 95% CI, 0.16-1.79). Conclusions: In this
exploratory analysis, the addition of adjuvant FP CTx appeared to favorably
affect the duration FFR only for patients with rectal cancer and intermediate
response to CXRT followed by radical resection. These data support the
investigation of the role for adjuvant fluoropyrimidine therapy among
patients with CR or IR and the addition of oxaliplatin for PR patients.
3558 General Poster Session (Board #26B), Mon, 8:00 AM-12:00 PM
Phase II study of combination therapy with S-1 and cetuximab in patients
with KRAS wild-type unresectable colorectal cancer who had previously
received irinotecan, oxaliplatin, and fluoropyrimidines (KSCC0901). Presenting
Author: Kazuma Kobayashi, Department of Medical Oncology,
Kochi Health Sciences Center, Kochi, Japan
Background: Anti-epidermal growth factor receptor (anti-EGFR) antibodies
alone or in combination with irinotecan (Iri) can be considered standard
third-line therapy for KRAS wild-type (wKRAS) unresectable colorectal
cancer (UNCRC). However, some UNCRC patients (pts) cannot tolerate
Iri-containing therapy. S-1, an oral fluorouracil (FU) derivative, enhances
the anti-tumor effect by inhibiting dihydropyrimidine dehydrogenase activity
and reducing digestive toxicity. Combination therapy with cetuximab
(C-mab) may restore 5-FU resistance in 5-FU–resistant CCs. Therefore, we
examined the efficacy of S-1�C-mab therapy in wKRAS UNCRC pts, who
had previously received Iri, oxaliplatin (OX), and FUs. Methods: The study
design was multicenter, single-arm, open-label phase II study. The major
inclusion criteria were written informed consent; histologically proven CRC
and clinically proven UNCRC; presence of measurable lesions; previous
therapy with Iri, OX, and 5-FU; documented progressive disease after
5-FU–based chemotherapy; wKRAS tumors; age � 20 years; performance
status (PS) 0–1; and adequate organ function. The treatment protocol was
as follows: weekly durable intravenous (DIV) C-mab administration at 400
mg/m2 (day 1) and 250 mg/m2 /week (except day 1) and oral administration
of 80 mg/m2 /day S-1 on days 1–28 of each 42-day cycle. The primary
endpoint was progression-free survival (PFS). A sample size of 39 was
planned for a threshold PFS of 3.5 months and expected value of 6.0
months, with one-sided alpha of 0.05 and beta of approximately 0.2.
Results: One patient was ineligible; 38 pts (PS 0/1, 32/6; 1/2/�3 prior
chemotherapy regimens, 4/23/11) were enrolled from 10/2009 to 12/
2010. The median PFS (central review) was 5.5 months (90% CI: 4.4 –
5.7); median overall survival (OS), 13.1 months; and the best ORR,
36.8%. The most common grade 3–4 adverse events were neutrophils,
hypokalemia, rash, and dry skin. Conclusions: This study showed that
S-1�C-mab may be a promising and well-tolerated treatment choice of
wKRAS UNCRC, who had previously heavily treated by Iri, OX and FUs.
Gastrointestinal (Colorectal) Cancer
3557 General Poster Session (Board #26A), Mon, 8:00 AM-12:00 PM
Post-progression survival (PPS) according to treatment line, type, and time
in phase III trials in advanced colorectal cancer (ACC). Presenting Author:
Marc E. Buyse, International Drug Development Institute, Louvain-la-
Neuve, Belgium
Background: Since post-progression therapy influences overall survival
(OS), PPS is of interest as a determinant of OS. We quantified the
relationship between several median times to event in ACC: progressionfree
survival (PFS), PPS and OS. We looked for factors with an impact on
these times. Methods: We searched PubMed for phase III trials published
between January 1998 and December 2010 in 12 leading journals. PPS is
the difference between median OS and median PFS or time to tumor
progression. The statistics of interest (median times [PFS, OS and PPS]
and the ratio of PPS/OS) were compared using t-tests. Results: We retrieved
70 trials that yielded 71 comparisons and 156 arms (one trial was factorial)
involving 38,504 patients. Trials from the period 2005-10 enrolled more
patients than trials from the period 1998-2004 (medians of 246 vs 174
per arm; P�.026). PPS could be calculated for 60 trials and 135 arms
(Table). Treatment type did not have an impact on any statistic. Treatment
line had a significant impact on all times and on the ratio of PPS/OS,
although the difference on the latter statistic was small. Treatment period
had a significant impact on all times but not on the ratio of PPS/OS.
Conclusions: None of the factors examined have a major impact on the ratio
of PPS/OS. This suggests that in ACC, gains in PFS are translated into
proportional gains in OS, one of the conditions required for PFS to be
considered a surrogate for OS.
PFS (months) PPS (months) OS (months) PPS / OS (%)
Trial type N Average* p Average* p Average p Average* P
Overall 135 6.3 - 9.0 - 15.3 - 59 -
Chemotherapy only
97 6.1 .30 9.0 .64 15.1 .43 59 .82
At least one targeted agent 38 6.6
9.3
15.9
59
1st line only
108 6.8 �.001 9.6 �.001 16.4 �.001 58 .004
2nd / 3rd line
27 4.0
7.0
11.0
63
Published 1998-2004
59 5.2 �.001 7.8 �.001 13.0 �.001 60 .51
Published 2005-2010 76 7.1
10.0
17.1
58
1st line, 1998-2004
51 5.5 �.001 8.2 �.001 13.7 �.001 59 .16
1st line, 2005-2010 57 8.0
10.8
18.8
57
2nd/3rd line, 1998-2004 8 3.1 .033 5.2 .016 8.3 .007 62 .74
2nd / 3rd line, 2005-2010 19 4.4
7.7
12.1
63
N, Number of treatment arms; * Average of median values for treatment arms.
217s
3560 General Poster Session (Board #27A), Mon, 8:00 AM-12:00 PM
Impact of body mass index (BMI) and weight changes on recurrence and survival
in stage III colon cancer (CC). Presenting Author: Joanna Vergidis, British
Columbia Cancer Agency, Vancouver, BC, Canada
Background: Research suggests that physical activity can lower the risk of relapse
and mortality from CC. It is unclear if such potential benefits are mediated
through an effect on weight. Our aims were to 1) evaluate the impact of
pre-treatment BMI on recurrence and survival in early stage CC, 2) examine how
weight gains and losses from baseline may affect outcomes, and 3) explore if the
effects of different body compositions are modified by adjuvant therapy (AT).
Methods: Patients (pts) diagnosed with stage III CC from 2006 to 2008,
evaluated at any 1 of 5 cancer centers in British Columbia, and who had their
weights measured serially throughout their AT period were reviewed. Using Cox
proportional hazards models, we compared outcomes among a) BMI�25
[normal] vs. 25-30 [overweight] vs. �30 [obese] and b) weight increase or
decrease of � vs. �/�5% and � vs. �/�10%, while controlling for confounders.
Results: A total of 821 pts were included: median age was 65 years, 50% were
men, and 83% were ECOG 0/1. At baseline, 43, 37, and 20% were normal,
overweight, and obese, respectively. Compared to pts with normal BMI, those
who were overweight or obese did not show an increased risk of recurrence (HR
0.81, 95%CI 0.42-1.58 and HR 1.09, 95%CI 0.48-2.51, respectively, p
trend�0.74) or death (HR 0.54, 95%CI 0.26-1.13 and HR 0.62, 95%CI
0.22-1.74, respectively, p trend�0.24). A number of pts experienced weight
gain or loss during their AT period, but none of these weight changes affected
outcomes (Table). Receipt of AT did not modify the effects of BMI or weight
change. In Cox models, advanced age and poor performance status were the
main factors that consistently correlated with an increased risk of recurrence and
death (p�0.05). Conclusions: Neither baseline BMI nor short-term weight
changes during AT appear to affect outcomes in stage III CC. Physical activity
likely exert its benefit on relapse and survival by influencing long-term weight
changes or acting via other alternative mechanisms.
Recurrence Death
% of Cohort HR p value HR p value
Weight gain
/�5% 50.4 1.04 0.90
/�10%
Weight loss
18.7 0.75 0.98
/�5% 12.4 0.98 1.42
/�10% 4.5 0.41 0.83
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