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

212s Gastrointestinal (Colorectal) Cancer
3536 General Poster Session (Board #22G), Mon, 8:00 AM-12:00 PM
Do we need adjuvant therapy in rectal cancer with complete pathologic
response (ypT0N0) after induction chemoradiation and laparoscopic mesorectal
excision? Presenting Author: Verónica Pereira, Department of Medical
Oncology, Hospital Clínic de Barcelona, Barcelona, Spain
Background: Neoadjuvant chemo-radiotherapy (CRT) is the standard of care
for patients (pts) with u�T3 by endoscopic ultrasound (EUS) rectal cancer.
Although pts with complete pathological response (ypT0N0) fare well in
multiple series, there is uncertainty of whether it’s due to the induction
(CRT), due to the adjuvant chemotherapy (ACT) or due to the combination
of both therapies. We have evaluated long-term outcomes in CRT-treated
pts. Those with ypT0N0, were not treated with ACT. Methods: Pts with
u�T3 rectal cancer, received neoadjuvant chemotherapy (225mg/m2/day
5-fluorouracil (FU)) in continuous infusion (CI) per 5 weeks (wks) and
concomitant radiotherapy (45 Gy). Laparoscopic surgery (LAP) was planned
after an interval of 5-8 wks. Pts achieving ypT0N0 were no treated with
ACT. Pts with ypT�1 or N1 were treated with 3 gr/m2 FU in 48 hour CI and
LV 200 mg/m2 every 2 wks x 6 cycles. Results: From November 2000 to
November 2008, a cohort of 173 pts were treated with induction CRT and
167 pts underwent total mesorectal excision (LAP, n�158, open surgery
n�9). Complete pathological response was achieved in 26/167 pts
(15.5%). After a median follow-up of 58.3 months, pts with ypT0N0 have a
5-year disease-free survival and overall survival rate of 96% (95% CI 76 to
99%) and 100% (95% CI not estimable) respectively. Conclusions: Using
these results, a clinical trial comparing observation versus adjuvant therapy
in ypT0N0 after standard CRT, would need to enroll 3088 pts to show a HR
of 0.75 in favor of ACT after 5 years of follow-up (alpha�.05, beta�.2). In
case that the true DFS lied in the lower bound of the 95% CI, 636 patients
would be needed under the same assumptions. These results do not
support the administration of ACT to ypT0N0 patients.
3538 General Poster Session (Board #23A), Mon, 8:00 AM-12:00 PM
Maintenance therapy with biweekly cetuximab (C) in the first-line treatment
of metastatic colorectal cancer (mCRC): The NORDIC 7.5 study
(NCT00660582), by the Nordic Colorectal Cancer Biomodulation Group.
Presenting Author: Per Pfeiffer, Department of Oncology, Odense University
Hospital, Odense, Denmark
Background: NORDIC 7.5 is a multi-center phase II trial of Nordic FLOX
plus biweekly C followed by maintenance C in first-line treatment of mCRC,
KRASwild-type (KRASwt). The aim was to complement the data of the
NORDIC VII trial, arm C (Tveit et al, ASCO GI 2011). Specifically, the goal
was to substantiate efficacy and safety of biweekly C as maintenance
therapy and to assess time to failure of strategy (TFS) as an end-point in
maintenance therapy studies. Methods: Patients had KRASwt, measurable,
non-resectable mCRC; no prior chemotherapy for metastases; WHO PS 0-2
and good organ function. Patients received 8 courses of FLOX (bolus
5FU/folinic acid days 1 � 2 with oxaliplatin day 1 every 2 weeks) plus
biweekly C (500 mg/m2 every 2 weeks) for 16 weeks followed by biweekly C
as maintenance therapy until progression (PD). After at least 2 months of
maintenance therapy, patients restarted FLOX plus biweekly C at the time
of RECIST PD, and continued until a second RECIST PD. The primary
endpoint was response rate (RR). Eighty-six patients were planned to
confirm a response rate of 60%. While awaiting the results of Nordic VII, we
amended the protocol to include 150 patients. Secondary endpoints
included PFS, OS, resection rate, and safety. TFS was an explorative
endpoint. Results: From July 2008 to September 2010, 152 KRASwt
patients were included in 11 Nordic centers. Results were updated
December 2011. Median age 64 years; 94% PS 0-1. RR 62%, median PFS
8.0 months, median OS 23.2 months, median TFS 11.9 months. Ten
patients (15%) had R0-resection of metastasis. FLOX � C was reintroduced
in 47 of 85 patients (55%) who were candidates for retreatment
and was started median 18 days after PD. Median duration of
re-introduction was 5 months (1-29), 9 patients (20%) had response.
Elevated baseline platelets and neutrofiles were associated with poor OS.
The most common grade 3/4 non-hematologic AEs in were diarrea (9%),
skin rash (9%), infection without neutropenia (7%), and fatigue (7%)
Conclusions: Maintenance therapy with biweekly cetuximab is an encouraging
strategy with efficacy and toxicity comparable to weekly cetuximab.
3537 General Poster Session (Board #22H), Mon, 8:00 AM-12:00 PM
Patterns of chemotherapy (CT) use in a U.S.-wide population-based cohort
of patients (pts) with metastatic colorectal cancer (mCRC). Presenting
Author: Thomas Adam Abrams, Dana-Farber Cancer Institute, Boston, MA
Background: Few population studies have examined treatment regimens
and duration in mCRC since the introduction of biologic therapies in 2004.
Methods: We assessed 4,877 consecutive mCRC pts who received CT
between Jan 2004 and Mar 2011 at academic, private, and community
hospital-based practices participating in a US-wide CT order entry (COE)
system that captures patient demographics, stage and treatment data.
Multivariate analyses of prospectively recorded patient and provider characteristics
identified significant predictors of specific therapeutic approaches.
Results: Among all pts, median age was 64; 55% male; (ECOG
PS 0/1/2�) (56%/33%/11%). In first-line CT, 17% of pts received
fluoropyrimidine (FU) only, while 16% received FU and irinotecan and
65% received FU and oxaliplatin. Older pts, those with poorer ECOG PS,
and those treated in private practices were significantly more likely to
receive FU only (all p �0.05). 53% of all pts received treatment in line 2,
28% in line 3, and 13% in line 4. Mean duration of treatment was 170 days
(line 1), 139 (line 2), 135 (line 3) and 126 (line 4). Bevacizumab (bev) was
administered to 65% of pts at some point in their treatment. Among the
51% who received bev in line 1, 33% continued bev beyond progression
(BBP) in line 2. Pts treated at academic centers, pts who received longer
duration of line 1 therapy, and pts whose providers had greater CRC pt
volume were significantly more likely to continue BBP. Overall, 23% of pts
received cetuximab (cet) (4% of all line 1 pts, 17% of line 2, 31% of line 3,
and 29% of line 4). Mean duration of cet use was 168 days (line 1), 125
(line 2), 133 (line 3) and 129 (line 4). Pts treated at academic centers, pts
who received longer duration of line 1 therapy, and pts treated in the West
US were significantly more likely to ever receive cet. Cet use decreased by
18% following FDA label change restricting use to KRAS wt pts in Jun
2009 (p �0.001). Of all pts, 6% received panitumumab at some point. Of
those, 39% had previously received cet. Conclusions: This populationbased
study provides insight into treatment patterns of mCRC in the US.
Usage of biologic agents varies significantly according to patient, practice,
and provider characteristics.
3539 General Poster Session (Board #23B), Mon, 8:00 AM-12:00 PM
Phase I study of EMD 525797 (DI17E6), an antibody targeting ���
integrins, in combination with cetuximab and irinotecan, as a second-line
treatment for patients with k-ras wild-type metastatic colorectal cancer.
Presenting Author: Elena Elez, Vall d’Hebron University Hospital, Barcelona,
Spain
Background: EMD 525797 is a humanized monoclonal antibody that
specifically targets all �� integrins, including ���1, ���3, ���5, ���6,
and ���8. In colorectal cancer (CRC), ���3 is highly expressed on
tumor-associated vessels, and ���5 is strongly expressed on tumor cells,
vessels, and stromal cells. Overexpression of ���6 is associated with a
significant reduction in median overall survival. Methods: Safety, tolerability,
and anti-tumor activity of escalating doses of EMD525797 in combination
with irinotecan and cetuximab were assessed in patients (pts) with
metastatic CRC who had failed first-line fluoropyrimidine/oxaliplatincontaining
chemotherapy. Pts received IV infusions over 1 hour of 250,
500, 750, and 1,000 mg EMD 525797 every 2 weeks in combination with
irinotecan at 180 mg/m2 IV every 2 weeks and cetuximab at 400 mg/m2 on
Cycle 1, Day 1 and then 250 mg/m2 IV weekly. A standard 3�3 trial design
was used. Three pts were enrolled at each dose level and if no dose limiting
toxicities (DLTs) were observed, pts were enrolled at the next dose level. An
additional 3 pts were added if 1 of the initial 3 pts in the cohort experienced
a DLT. Results: A total of 16 pts received treatment.No DLTs were observed
at any dose of EMD 525797 in combination with irinotecan and cetuximab.
Serious adverse events related to EMD 525797 included Grade 3 hypokalemia
and tachyarrhythmia. Dosing was well tolerated over treatment intervals
as long as 18 months. Objective responses included 1 partial response
(PR) at 250 mg; 1 complete response and 1 PR at 750 mg; and 2 PRs at
1,000 mg. Two pts had prolonged stable disease lasting longer than 11
weeks at 750 mg. Anti-tumor activity was observed in pts who had failed
anti-VEGF therapy in combination with first-line chemotherapy. Conclusions:
The combination of EMD 525797 with irinotecan and cetuximab was well
tolerated and has anti-tumor activity. Further evaluation of this regimen is
warranted and is underway in an open-label, randomized phase II study of
two doses of EMD 525797 (500 and 1,000 mg) combined with irinotecan
and cetuximab that are compared with standard irinotecan and cetuximab.
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