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

236s Gastrointestinal (Colorectal) Cancer
3633 General Poster Session (Board #38F), Mon, 8:00 AM-12:00 PM
Triplet chemotherapy (TC) with FOLFIRINOX regimen in metastatic colorectal
cancer (mCRC): Experience of the Val d’Aurelle Center. Presenting
Author: Emmanuelle Samalin, Digestive Oncology CRLC Val d’Aurelle,
Montpellier, France
Background: TC is a treatment option for mCRC to improve the tumor
response rate in selected patients (pts) and the conversion rate of initially
non-resectable liver metastases. The aim of this study was to evaluate the
impact and feasibility of FOLFIRINOX regimen in mCRC pts. Methods: All
mCRC pts with non-resectable disease who have received FOLFIRINOX
alone or combined with targeted therapies (bevacizumab or cetuximab)
from October 2000 to December 2010 were selected for this analysis.
Clinical data were collected in a mCRC specific data base and analyzed by
the end of 2011. Results: Ninety two pts (52% of men), median age 59 yrs
(range: 27-76) were treated with FOLFIRINOX (D1 oxaliplatin 85 mg/m² IV
2H then irinotecan 180 mg/m² IV 90 min and elvorin 200 mg/m², then 5FU
200 mg/m² and 2400 mg/m² by 46H infusion, D1�D15) alone (64%) or
combined with cetuximab(30%) or bevacizumab (6%), as 1st-line in 82 pts
(89%). Prophyllactic G-CSF was given in 58% of them. Primary tumor was
located in colon (58%) or rectum (42%), and 64 (69%) of pts presented
with synchronous metastases: liver 100%, lung 40%, peritoneum 17% and
nodes 17%. Median number of cures was 8 (range: 1-12). There was 1
toxic death. Grade 3-4 toxicities were: diarrhea 22%, neuropathy 21%,
cutaneous 12%, neutropenia 28%, febrile neutropenia 0%, thrombopenia
6%. Objective Response rate according to RECIST criteria was 72%
[CI95% 61-81] including 10 pts with complete response (11%). The
primary tumor was resected in 70 pts (76%) and 14% had KRAS mutated
tumor. Among the pts with liver metastases, 63 (68%) pts were evaluated
for secondary resectability by a multidisciplinary committee and 40 pts
(43%) had resection achieved (70% R0). Median overall survival was 49
months [CI95%28-62]. Conclusions: These results confirm the feasibility
of FOLFIRINOX regimen with or without targeted therapies and its efficacy
in terms of response rate and overall survival as 1rst-line treatment in
selected mCRC pts.
TPS3635^ General Poster Session (Board #38H), Mon, 8:00 AM-12:00 PM
MAVERICC: A randomized phase II study of mFOLFOX6-bevacizumab (BV)
versus FOLFIRI-BV with prospective biomarker stratification in previously
untreated metastatic colorectal cancer (mCRC). Presenting Author: Sachdev
P. Thomas, Illinois Cancer Care, Peoria, IL
Background: The identification of prognostic and predictive biomarkers
could significantly improve the risk-benefit ratio and cost-effectiveness of
1st-line mCRC regimens. This is the first prospective study of tumoral
ERCC1 (chemo-resistance marker to platinum compounds) and plasma
VEGF-A as potential biomarkers for oxaliplatin- and BV-containing regimens,
respectively, in an effort to further define the optimal chemotherapy
backbone with biologic therapies, including BV, for mCRC. Methods: In this
randomized, open-label, global, phase II study, patients (N�360) with
histologically or cytologically confirmed CRC and �1 measurable metastatic
lesion are stratified at screening by tumoral ERCC1 mRNA expression
(high vs low, cutoff of 1.7 [ERCC1/�-actin mRNA]). Eligibility criteria
include completion of adjuvant therapy �12 months before screening and
an ECOG performance status �1. Blood samples are collected to quantify
plasma VEGF-A levels. Patients within each ERCC1 stratification group are
randomized 1:1 to mFOLFOX6-BV or FOLFIRI-BV administered in 2-week
cycles. BV will be given at a dose of 5 mg/kg IV q2w. Patients will remain on
study treatment until disease progression (PD) or unacceptable toxicity. If
oxaliplatin or irinotecan need to be discontinued, BV and 5-fluorouracil or
capecitabine are to be continued until PD. The primary objectives are: 1) to
assess ERCC1 and VEGF-A as biomarkers of progression-free survival (PFS)
for oxaliplatin- and BV-containing regimens in 1st-line mCRC, and 2)
within ERCC1 high patients, to test whether FOLFIRI-BV is associated with
a prolonged 1st-line PFS compared to mFOLFOX6-BV. Secondary objectives
include assessing the impact of these markers on overall survival,
objective response, hepatic metastases resection, and safety. Exploratory
endpoints include correlative analyses with additional tumor tissue, blood,
and SNP markers. The first patient was enrolled in August 2011. An
interim biomarker distribution assessment of the first 100 patients is
planned, and the evaluation of the primary endpoints is estimated for early
2015. Clinicaltrials.gov: NCT01374425.
TPS3634 General Poster Session (Board #38G), Mon, 8:00 AM-12:00 PM
A randomized, double-blind, phase (Ph) III study of the irinotecan-based
chemotherapy FOLFIRI plus ramucirumab (RAM) or placebo (PL) in
patients (pts) with metastatic colorectal carcinoma (mCRC) progressive
during or following first-line therapy with bevacizumab (BEV), oxaliplatin
(OXALI), and a fluoropyrimidine (FP) (RAISE) (NCT01183780). Presenting
Author: Axel Grothey, Mayo Clinic College of Medicine, Rochester, MN
Background: Vascular endothelial growth factor (VEGF) and the VEGF
receptor-2 (VEGFR-2) regulate angiogenesis and are overexpressed in CRC.
RAM is a fully human IgG1 monoclonal antibody that inhibits binding of
VEGF ligands to VEGFR-2 and inhibits VEGFR-2 activation and signaling.
In a preclinical study, antiangiogenic and antitumor effects were observed
when DC101, an antibody that targets murine VEGFR-2, was administered
to mice bearing human colon cancer xenografts. Antitumor activity for RAM
has been demonstrated in a Ph I study in pts with solid tumors over a wide
range of RAM dose levels and in a Ph II study with RAM � mFOLFOX-6 as
1st-line therapy in pts with mCRC. Methods: This ongoing, randomized,
double-blind, placebo-controlled Ph III study includes mCRC pts with
measurable or nonmeasurable disease and ECOG performance status of
0-1 who have experienced disease progression during or within 6 months
following 1st-line therapy with BEV, OXALI, and any FP. Randomization is
stratified by geographic region, KRAS status, and time to progression after
initiation of 1st-line therapy. Pts are randomized 1:1 to either RAM 8 mg/kg
or PL every 14 days. Pts in both arms receive FOLFIRI (irinotecan: 180
mg/m2 , folinic acid: 400 mg/m2 , 5-fluorouracil: 400 mg/m2 bolus followed
by 2400 mg/m2 continuous infusion over 46-48 hours). The primary
endpoint is overall survival (OS). The sample-size estimate assumes 85%
power to detect at least a 2.5-month median OS difference (HR � 0.8)
between treatment arms with a 1-sided alpha of 0.025. Secondary
endpoints include progression-free survival, tumor response, safety, pharmacokinetics,
immunogenicity, and correlations between biomarkers and
clinical outcome. CRC tissue and blood collection is mandatory for
biomarker analyses. As of 05 January 2012, 238 of 1050 planned pts have
been enrolled from 100 sites in North America, South America, Europe,
Asia, and Australia.
TPS3636 General Poster Session (Board #39A), Mon, 8:00 AM-12:00 PM
TRICC-c: BIBF 1120 versus placebo in patients receiving oxaliplatin plus
fluorouracil and leucovorin (mFOLFOX6) for advanced, chemorefractory
metastatic colorectal cancer (mCRC)—A multicenter, randomized phase II
trial in progress. Presenting Author: Andreas Berger, Department of
Internal Medicine I, Martin-Luther-University Halle-Wittenberg, Halle,
Germany
Background: Colorectal cancer (CRC) is the second leading cause of
cancer-related death in western countries. With advances in the treatment
of metastatic CRC (mCRC) in the last decade using combination chemotherapy
and bevacizumab, a monoclonal antibody against the vascular
endothelial growth factor (VEGF), progression free survival (PFS) in first
and second line setting was substantially improved. Tumour angiogenesis
is also driven by other factors but VEGF including Platelet Derived Growth
Factor (PDGF) and Fibroblast Growth Factor (FGF). BIBF1120 is a potent,
orally available triple angiokinase inhibitor that blocks the receptor tyrosine
kinase activity of human VEGFR1-3, FGFR1 and -3 and PDGFR� and -�.
Thus, BIBF1120 could be an exciting addition to the treatment of patients
with chemorefractory CRC. Methods: Randomized, double-blind, placebocontrolled,
multicentre, phase II trial of BIBF1120 (orally, 200 mg, bid,
d1-d14, Arm A) vs. placebo (Arm B) in patients receiving mFOLFOX6
(oxaliplatin, 85 mg/m2 , fluorouracil, 400 mg/m2 bolus and 2400 mg/m2 over 46 h, leucovorin, 200 mg/m2 ) q14 d for patients (ECOG performance
status 0-1) with chemorefractory mCRC who received one prior line of
chemotherapy. Scheduled are 90 patients per treatment arm. Primary
endpoint: PFS, Secondary endpoints: objective response, overall survival,
duration of overall response, safety. Additionally there will be an explorative
analysis of predictive biomarkers for BIBF1120. 4 of planned 180 patients
have been enrolled. We expect the last patient out in June 2013. (Trial
identifier: NCT01362361.)
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