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

3540 General Poster Session (Board #23C), Mon, 8:00 AM-12:00 PM
Prospective study of EGFR intron 1 CA tandem repeats to predict factor
benefit from cetuximab and irinotecan. Presenting Author: Carlotta Antoniotti,
U.O. Oncologia Medica 2, Azienda Ospedaliero-Universitaria Pisana,
Istituto Toscano Tumori, Pisa, Italy
Background: Retrospective experiences have investigated the potential
influence of EGFR intron 1 CA repeats on the efficacy of cetuximabcontaining
treatments. Different series, adopting different criteria to define
short (S) and long (L) variants, have provided contrasting results. Methods:
We designed a prospective confirmatory study, to detect a HR for PFS of
1.75 for L- compared to SS genotypes in a population of KRAS and BRAF
wild-type irinotecan-resistant mCRC pts treated with cetuximab and
irinotecan. Estimating a prevalence of 60% of the SS variant and setting a
two-sided alfa�0.05 with a power of 80%, 104 events were required. We
defined S and L allelic variants those presenting � and �20 CA repeats,
respectively. EGFR (CA) n repeat polymorphism was assessed following a
5’-end [�-33P] ATP-labeled PCR protocol. Results: One-hundred-fifteen pts
were included. At a median follow up of 21.9 months, PFS and OS were 5.2
and 13.4 months, respectively. Thirty-three (29%) out of 114 evaluable
pts achieved response. EGFR (CA) n repeat genotype was L- and SS in 45
(40%) and 68 (60%) out of 113 evaluable cases. No differences in PFS or
OS were observed between L- and SS genotypes (median PFS: 4.4 vs. 5.3
months, HR: 1.00 [95%CI: 0.67-1.51], p�0.991; median OS: 11.3 vs.
14.2 months, HR: 1.30 [95%CI: 0.80-2.22], p�0.261). Ten (22%) out of
45 L- pts achieved response compared to 22 (33%) out of 67 SS pts
(Fisher’s Exact test: p�0.617). Other exploratory analyses adopting
different cut-off values reported in literature led to similar results.
Conclusions: This prospective study, including a clinically homogenous and
molecularly selected population, does not confirm any predictive or
prognostic effect for EGFR (CA) n repeat allelic variants with respect to the
efficacy of cetuximab and irinotecan in advanced lines of treatment. The
present experience strengthens the need of prospectively challenging
retrospective findings, as an essential step on biomarkers’ way toward
clinical practice.
3542 General Poster Session (Board #23E), Mon, 8:00 AM-12:00 PM
Utilization and outcomes of primary tumor surgery for stage IV colon cancer
in the United States: A population-based study. Presenting Author: Yvonne
Sada, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX
Background: Stage IV colon cancer treatment may include resection of the
primary tumor. Current use of primary tumor surgery (PTS) in clinical
practice is unknown. This study examined utilization and determinants of
PTS and evaluated its effect on survival. Methods: Using national Surveillance,
Epidemiology, and End Results registry data, stage IV colon cancer
patients diagnosed from 1998-2008 were identified. Data on demographics,
PTS, and tumor features were collected. Temporal changes in receipt of
PTS were examined over 3 periods (1998-2000, 2001-2004, 2005-
2008). Multiple logistic regression was used to identify significant determinants
of PTS. 1- and 3-year cancer-specific survival was calculated in PTS
and non-PTS patients. Cox proportional hazards models examined the
effect of PTS on mortality risk. Results: 16,029 patients were identified.
Median age was 69 (IQR: 57-78), and 50% were male. Approximately 67%
of patients received PTS. Receipt of PTS significantly declined from 72%
in 1998-2000 to 68% in 2001-2004, and 63% in 2005-2008 (p�0.01).
Results from the logistic regression analysis showed that patients who were
younger, white, married, had right sided cancer and higher tumor grade
were more likely to receive PTS (all p�0.01). The 1- and 3-year survival
was higher in patients who received PTS compared with those who did not
(1-year: 55% (95% CI: 54-56) vs. 24% (95% CI: 23-26); 3-year: 19%
(95% CI: 19-20) vs. 4% (95%CI: 3.4-4.9)). Adjusted for demographics
and tumor features, risk of mortality was 54% (HR�0.46; 95% CI:
0.44-0.48) lower in patients who received PTS than those without PTS.
Recent year of diagnosis (HR�0.88; 95% CI: 0.75-0.80) and being
married (HR�0.90, 95% CI: 0.86-0.95) were associated with lower
mortality. Older age (HR�1.48; 95% CI: 1.39-1.56), black race (HR�1.09;
95% CI: 1.03-1.15), right sided cancer (HR�1.21; 95% CI: 1.17-1.26),
and poorly differentiated tumors (HR� 1.62; 95% CI: 1.46-1.80) were
associated with increased mortality. Conclusions: PTS utilization for stage
IV colon cancer has significantly declined, yet survival was higher in
patients who received PTS. However, these findings are limited by the
absence of co-morbidity and chemotherapy data.
Gastrointestinal (Colorectal) Cancer
213s
3541 General Poster Session (Board #23D), Mon, 8:00 AM-12:00 PM
Capecitabine (cape)-associated hand-foot skin reaction (HFS) as a clinical
predictor of improved survival in patients (pts) with colorectal cancer.
Presenting Author: Ralf Hofheinz, Day Treatment Centre at the Interdisciplinary
Tumour Centre Mannheim, Universitätsmedizin Mannheim, Mannheim,
Germany
Background: HFS is frequently observed during treatment with cape. Post
hoc analyses of the X-ACT trial suggested that HFS may be associated with
improved prognosis in cape recipients in stage III colon cancer. In the
present analysis we evaluated the potential association of HFS and survival
in pts with metastatic colorectal cancer and locally advanced rectal cancer.
Methods: Pts receiving cape within AIO KRK-0104 and Mannheim rectal
cancer trials were analyzed. HFS was graded according to NCI-CTC. Time to
first occurrence of HFS was described per cycle and HFS developing during
cycles 1 and 2 was defined as “early HFS”. Baseline characteristics in the
groups of pts with or without HFS were compared using standard tests.
Toxicities observed in both groups were compared with Fisher’s exact test.
Progression-free (PFS) or disease-free (DFS) and overall survival (OS) data
from both trials were pooled and the HFS group was compared to the
non-HFS using Kaplan-Meier analysis. Results: A total of 374 pts are
included, of whom 29.3% developed HFS. Of these, 70.9% had “early
HFS”. Baseline characteristics were comparable between the HFS and the
non-HFS groups concerning age, gender, ECOG status and UICC stage. On
multivariate analysis none of these factors had influence on the occurrence
of HFS. The percentage of all-grade hematological toxicities did not differ
between both groups. Contrarily, patients in the HFS group had a
significantly higher rate of all grade (but not grade 3-4) diarrhea, stomatitis/
mucositis and fatigue (p�0.01 resp.). Moreover, pts in the HFS group had
improved PFS/DFS (29.0 vs. 11.4 months; p�0.015, HR 0.69) and OS
(75.8 vs. 41.0 months; p�0.001, HR�0.56). Within the HFS group the
PFS/DFS and OS were comparable between pts in the “early” and the “late
HFS” groups. Conclusions: This analysis provides further evidence for the
association of HFS and survival in patients with colorectal cancer. Baseline
characteristics and the time of occurrence of HFS had no impact on
survival. Patients developing HFS had a higher probability of developing
any-grade gastrointestinal toxicity and fatigue while no correlation with
hematological toxicity was noticed.
3543 General Poster Session (Board #23F), Mon, 8:00 AM-12:00 PM
Phase Ib study of dulanermin combined with FOLFIRI (with or without
bevacizumab [BV]) in previously treated patients (Pts) with metastatic
colorectal cancer (mCRC). Presenting Author: Saifuddin M. Kasubhai,
Northwest Medical Specialties, Tacoma, WA
Background: Dulanermin is a recombinant soluble human Apo2 ligand/TNFrelated
apoptosis-inducing ligand (Apo2L/TRAIL) that activates apoptotic
pathways by binding to the pro-apoptotic death receptors DR4 and 5. This
is the final update of the study assessing the safety of dulanermin
combined with FOLFIRI (� BV) in previously treated mCRC pts. Methods:
This was a multicenter, open-label, dose-escalation and cohort expansion
study. Dulanermin was administered intravenously in 14-day cycles on
Days 1, 2 and 3 at 9 mg/kg or 18 mg/kg, with FOLFIRI (� BV in pts not
previously treated with BV) on Day 1. Dose-limiting toxicity (DLT) was
assessed through 2 cycles (28 days). Adverse events (AE) were recorded
through all cycles. Response was assessed with RECIST (v1.0). Results: A
total of 27 pts received 1-48 cycles (median 10) of dulanermin with
FOLFIRI (1 pt received BV). No DLTs were reported and no relationship
between dulanermin dose level and AE incidence or severity was detected.
The most frequent AEs reported as dulanermin-related were fatigue (37%),
anemia (19%), diarrhea, nausea, stomatitis, and weight decreased (15%
each). The most frequent Grade �3 AEs reported as dulanermin-related
were fatigue (15%), anemia, febrile neutropenia and vomiting (7% each).
Serious AEs reported as dulanermin-related included: vomiting, dehydration,
and febrile neutropenia (1 pt each). Some of these events were
reported as related to dulanermin and other study drugs. One pt died on
study due to disease progression. Other reasons for discontinuation of study
treatment included disease progression (21 pts, 78%), and physician’s
decision and pt’s decision (2 pts each, 7%). One pt is still receiving
treatment. Among the 27 pts, best responses included 6 (22%) partial
responses (5 confirmed, 1 unconfirmed), 17 (63%) stable disease, 3
(11%) progressive disease and 1 (4%) pt with no on-study tumor assessment.
Conclusions: The addition of dulanermin to FOLFIRI (� BV) was well
tolerated in previously treated mCRC pts. AEs were similar to those
previously reported for the chemotherapy alone. Tumor responses were
consistent with treatment response to FOLFIRI in this patient population.
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