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

4017 Poster Discussion Session (Board #9), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Maintenance sunitinib (MS) or observation (O) in metastatic pancreatic
adenocarcinoma (MPA): Clinical and translational results of a phase II
randomized trial (NCT00967603). Presenting Author: Michele Reni, San
Raffaele Scientific Institute, Milan, Italy
Background: Combination chemotherapy (CT) prolonged progression-free
survival at 6 months (PFS6) of patients (pts) with MPA from �20% with
gemcitabine (GEM) to �50%. To prolong CT over 6 months has unproven
benefit and is hampered by cumulative toxicity. This open-label, randomised,
multi-centre phase II trial explored the role of MS in pts with MPA
without progressive disease (PD) after CT, using an O group as calibration
arm. The role of circulating endothelial cells (CEC) as biomarker of MS
activity was explored. Methods: Adult pts with pathologic diagnosis of MPA,
performance status (PS) �50%, without radiological PD or CA19.9 raise
�20% after 6 months of CT were stratified based on PS and previous CT
and randomized to O (arm A) or MS at 37.5 mg daily until PD or a maximum
of 6 months (arm B). Primary endpoint was PFS6. Sample size (H0 10%;
H1 30%; a .10; b .10) was 26 pts per arm and MS had to be considered of
interest with �5 pts PFS6. CEC were evaluated by flow cytofluorometry on a
baseline peripheral blood sample. Results: 56 pts (29 arm A; 27 arm B)
were enrolled. One arm B pt had kidney cancer and was excluded. Pts
characteristics were (A/B): median age 64/61 years; median PS 90/100;
median CA19.9 45/32; previous CT: GEM 3/3; combination CT 26/22.
Main grade 3-4 toxicity in arm B was 15% neutropenia; 12% thrombocytopenia
and hand-foot syndrome, 8% diarrhea. Second line CT was given to
76% of pts in both arms. One arm A (3%) and 6 arm B pts (23%; p�.01)
were PFS6; 2y overall survival (OS) was 4% and 25% (p�.09). Blood
sample for CEC analysis was available for 46 of 55 pts (84%). In arm A,
median PFS was longer for pts with CEC number �30 (lower terzile group)
when compared to �30 (2.9 versus 1.9 months; p.08). MS significantly
increased PFS in CEC �30 group (3.4 months; p�.01). No PFS difference
between arms was observed in �30 group (2.3 months). Conclusions: This
is the first randomized trial on maintenance therapy in MPA. In arm B, the
primary endpoint was fulfilled and 2y OS was remarkably high, suggesting
that MS may have a role in pts with MPA. The number of CEC may be useful
to predict benefit from MS.
4019 Poster Discussion Session (Board #11), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Dual blockade of epidermal growth factor receptor (EGFR) and insulin-like
growth factor receptor-1 (IGF-1R) signaling in metastatic pancreatic
cancer: Phase I/randomized phase II trial of gemcitabine, erlotinib, and
cixutumumab versus gemcitabine plus erlotinib (SWOG-0727). Presenting
Author: Philip Agop Philip, Karmanos Cancer Institute, Wayne State
University, Detroit, MI
Background: Targeting a single pathway in pancreatic adenocarcinoma
(PAC) is unlikely to impact its natural history. EGFR targeting with erlotinib
added to gemcitabine (G) marginally improved the outcome of patients with
advanced disease. We tested the hypothesis that if the EGFR and IGF-1R
pathways are simultaneously blocked then progression free survival (PFS)
would be significantly improved by abrogating reciprocal signaling that
leads to resistance to either drug. Methods: This was a phase I/randomized
phase II (RP2) study testing the anti-IGF-1R monoclonal antibody cixutumumab
combined with erlotinib and G in patients with metastatic PAC. The
control arm was erlotinib plus G. The primary endpoint of the RP2 portion
of the study was PFS. Eligibility included patients with untreated metastatic
disease, performance status 0/1, fasting blood glucose less than
institutional upper limit of normal, and willingness to provide tissue and
blood specimens for correlative studies. Results: In phase I portion (n�10)
safety of cixutumumab 6 mg/kg IV/wk, erlotinib 100 mg/day orally and G
1000 mg/m2 IV D 1, 8, and 15 of a 28-day cycle was established. In the
RP2 portion (n�124) 114 eligible patients (median age 63) were included.
On the cixutumumab arm, 59% of patients were female vs. 40% on
control arm. Median PFS and overall survival were 3.7 and 6.7 months,
respectively, in both arms of the study. Major grade 3 and 4 toxicities were
(cixutumumab/control) elevation of transaminases (12%/6%), fatigue
(16%/12%), gastrointestinal (35%/28%), neutropenia (21%/10%), and
thrombocytopenia (16%/7%). Grade 3/4 hyperglycemia was seen in 16%
of patients on cixutumumab. Grade 3 or 4 kin toxicity was similar in both
arms of the study (� 5%). Five treatment-related deaths were reported: 2
cardiac on each arm, 1 pulmonary on cixutumumab. Conclusions: IGF-1R
inhibitor cixutumumab did not improve the progression free or overall
survival of patients with metastatic PAC treated with erlotinib and G in a
molecularly unselected population.
Gastrointestinal (Noncolorectal) Cancer
243s
4018 Poster Discussion Session (Board #10), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
FOLFIRI.3 (CPT-11 plus folinic acid plus 5-FU) alternating with gemcitabine
or gemcitabine (G) alone in patients (pts) with previously untreated
metastatic pancreatic adenocarcinoma (MPA): Results of the randomized
multicenter AGEO phase II trial FIRGEM. Presenting Author: Isabelle
Trouilloud, Hôpital Européen Georges Pompidou, Paris, France
Background: CPT-11 showed modest activity and tolerability in MPA. We
developed a new strategy to improve efficacy and tolerability of CPT-11
based regimen in MPA pts. Methods: Chemotherapy-naive pts with histologically
proven MPA, bilirubin levels � 1.5 ULN and performance status (PS)
0-1 were randomized in a phase II trial to receive either FOLFIRI.3 (CPT-11
90 mg/m2 as a 60-min infusion on day (D) 1, leucovorin 400 mg/m2 as a
2-hr infusion on day 1, followed by 5-FU 2000 mg/m2 as a 46-hr infusion
and CPT-11 90 mg/m2 , repeated on D3, at the end of the 5-FU infusion,
every 2 weeks) for 2 months alternarting with G (1000 mg/m² at a fixed
dose rate of 10 mg/m²/min on D1, D8, D15, D29, D36 and D43) for 2
months (arm A) or G alone (arm B). Using Fleming design the primary end
point was rate of progression free survival (PFS) at 6 months from (H0)
25% over (H1) 45% needing to include 49 pts/arm. Results: Between 2007
and 2011, 98 pts were enrolled (males: 59, median age: 62 years, PS 0:
32%). Median follow-up was 23 months. Grade 3-4 toxicities per pts (%) in
arm A/B were diarrhea 13/0, nausea-vomiting 11/4, neutropenia 51/25
and febrile neutropenia 4/0. No toxic death occurred. Response rate were
40 and 11% as disease control rate (CR�PR�SD) were 73 and 52% in arm
A and B, respectively. The primary endpoint of the trial was met with rate of
PFS at 6 months of 48% (95% CI: 33-63) in arm A while in arm B PFS was
30% (95% CI: 17 - 44). One year PFS was 23% (95%CI: 11.5-36) and
11% (95%CI: 4-21), respectively. Conclusions: FIRGEM strategy is feasible
and efficient with a manageable toxicity profile in good condition pts
with MPA. A phase III trial comparing this strategy with the FOLFIRINOX
triplet therapy focusing on quality of life should now be performed.
4020 Poster Discussion Session (Board #12), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Long-term survival in patients with pancreatic cancer: Relevant factors in
CONKO-001. Presenting Author: Marianne Sinn, Medical Department,
Division of Hematology, Oncology and Tumor Immunology Charité -
Universitätsmedizin Berlin, Berlin, Germany
Background: Long-term survival (LTS) in patients with pancreatic cancer is
still rare, even in resectable and potentially curative stages. Few prospective
data are available to identify predictive factors. The CONKO-001 study
establishing adjuvant gemcitabine (GEM) may provide data to answer this
question. Methods: CONKO-001 patients (pts) with an overall survival � 5
years were included in this analysis and compared to those with � 5 years.
Central re-evaluation of the primary histology was done to confirm the
diagnosis of pancreatic adenocarcinoma. Univariate analysis with the
x²-test identified qualifying factors (p�0.10). Logistic regression with a
stepwise selection process was used to investigate the influence of these
covariates on LTS. Results: Of the 354 pts included in the intention-to-treat
analysis of CONKO-001, 53 (15%) pts with an overall survival of more than
5 years could be identified, for 39 (74%) tumor specimens could be
obtained. In 38 (97% of pts with LTS) the diagnosis of adenocarcinoma
was confirmed, 1 showed a high-grade neuroendocrine tumor. Relevant
factors for all 53 pts with LTS compared to remaining 301 non-LTS pts in
univariate analysis were active treatment (GEM) (68% in LTS pts vs 48% in
non-LTS pts; p�0.006), tumor grading (G1 17% vs 3%, G2 64% vs 55%,
G3 17% vs 40%; p�0.000), tumor-size (T2 15% vs 9%, T3 74% vs 84%;
p�0.004) and lymph nodes (N0 47% vs 25% N1 53% vs 74%; p�0.003.
Significance could not be demonstrated for resection margin (R0 vs R1),
sex, age, Karnofsky performance status (�80% vs 80% vs �80%) and CA
19-9 (40-100 U/ml vs �40 U/ml) at study entry. In the multivariate
analysis tumor grading (gr) (odds ratio gr 3 vs gr 1�0.07; gr 3 vs gr 2�
0.38; p�0.017) and active treatment (odds ratio GEM vs observation�0.38;
p�0.004) were the only independent prognostic factors.
Conclusions: Long-term survival can be achieved in adenocarcinoma of the
pancreas. In pts with completely resected pancreatic cancer, tumor grading
and active treatment with GEM were the only predictive factor for LTS.
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