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

4043 General Poster Session (Board #41B), Mon, 8:00 AM-12:00 PM
Phase I/II study of 90Y-clivatuzumab tetraxetan ( 90Y-hPAM4) combined
with gemcitabine (Gem) in advanced pancreatic cancer (APC): Final
results. Presenting Author: Allyson J. Ocean, New York Presbyterian
Hospital-Weill Cornell Medical College, New York, NY
Background: A Phase I/II trial evaluated single and repeated cycles of
fractionated radioimmunotherapy (RAIT) with 90Y-labeled humanized mAb
( 90Y-hPAM4) plus Gem as first-line therapy in Stage 3-4 APC. Methods:
Cycles of Gem once-weekly x 4 with 90Y-hPAM4 on wks 2, 3 and 4 were
repeated until progression, withdrawal or unacceptable toxicity. In Part I,
90 2 Y doses were escalated with Gem fixed at 200 mg/m . In Part II, Gem was
increased up to 1000 mg/m2 , with 90Y fixed at 12 mCi/m2 for cycle 1 and
lowered for retreatment. Results: Of 100 pts entered, 10 withdrew early,
while 90 (73 stage IV) received 1-4 cycles. In Part I, 38 pts received
90 2 Y-hPAM4 weekly x3at6.5, 9, 12, or 15 mCi/m , with the same cycle
repeated 1-3 times in 13 pts. By CT-RECIST criteria, 6 pts (16%) had PRs
and 16 (42%) had stabilization as best response (58% disease control).
After cycle 1, 52% (13/25) with PET-avid images had �25% SUV
reduction, and 33% (9/27) with elevated CA19-9 levels decreased by
�50%. The median OS was 7.7 mo., but 11.8 mo. for retreated pts [46%
(6/13) survived �1 yr.], and with improved efficacy at higher 90Y doses.
NCI-CTCv3 Grade 3-4 platelets or ANC developed in 20/38 (53%) after
cycle 1 (all reversible to Grade 1) and in all retreated pts (irreversible in 4/9
pts at 12 or 15 mCi/m2 ). In Part II, 52 pts received increased Gem without
evidence of improved efficacy, while 13 pts were retreated with more
acceptable toxicity at lower 90Y doses of 6.5 or 9 mCi/m2 . Treatment was
well tolerated with no infusion reactions. Infections requiring IV antibiotics
occurred at a low rate and responded to appropriate coverage (bacteremia/
sepsis, 7%; febrile neutropenia, 4%; ascending cholangitis, 3%; pneumonia,
2%; others 1%). One case of bleeding occurred, due to rectal tumor
invasion. Anecdotal reports of good performance and decreased pain
medication requirements require further validation. Conclusions: Fractionated
RAIT with 90Y-hPAM4 combined with low-dose 200 mg/m2 GEM
appears promising as a treatment regimen for APC. Hematologic toxicity
was dose limiting. A 90Y-hPAM4 dose of 12 mCi/m2 for cycle 1 and 6.5
mCi/m2 for cycle 2 have been selected as suitable for further clinical
development in the first-line setting.
4045 General Poster Session (Board #41D), Mon, 8:00 AM-12:00 PM
A phase II multi-institutional study to evaluate gemcitabine and fractionated
stereotactic body radiotherapy for unresectable, locally advanced
pancreatic adenocarcinoma. Presenting Author: Joseph M. Herman, Sidney
Kimmel Comprehensive Cancer Center at Johns Hopkins University,
Baltimore, MD
Background: Phase I/II studies with single-fraction (25 Gy) stereotactic
body radiotherapy (SBRT) for pancreatic ductal adenocarcinoma (PDA)
have shown local progression free survival (LPFS) rates of �90%, but are
limited by late GI toxicity and minimal tumor response. We performed a
phase II multi-center trial of gemcitabine (GEM) and fractionated SBRT to
determine if a high rate of LPFS with reduced toxicity could be achieved.
Methods: After multidisciplinary review, 32 pts with locally advanced PDA
received GEM in sequence with SBRT (6.6 Gy in 5 consecutive daily
fractions, 33 Gy total). LPFS, metastasis free survival (MFS), and overall
survival (OS) were measured from date of tissue diagnosis. Objective tumor
response (OTR) was assessed by RECIST/PERCIST. EORTC QLQ-C30/
PAN26 questionnaires were used to measure QOL. Results: Median f-up
was 12 mos (range, 2-23). Mean age was 69.9 yrs (SD, 9.8) and 62% were
male. Pts received a mean of 2.2 (SD, 1.0) GEM doses prior to SBRT and
8.3 (SD, 5.6) doses total. All pts completed SBRT. Median OS was 15.9
months (95% CI, 12.7-18.8). Stratification by CA19-9 � or � 90 at
diagnosis yielded a hazard ratio of 6.2 for � 90 (p�0.021). Median LPFS
has not been reached and median MFS was 10.2 mos (95% CI, 2.9-17.5).
LPFS rate at 1 year was 87%. OTR on CT was seen in 41%, while 41% had
stable disease and 18% progressed. Tumor metabolic activity decreased in
17/18 patients with pre/post-SBRT PET available. Mean peak SUV was 4.0
pre-SBRT versus 2.4 post-SBRT (p�0.002). Median CA19-9 was reduced
from 124.7 prior to SBRT to 43.9 afterwards. Acute toxicity included:
grade 2 anorexia (37%), fatigue (28%), nausea (22%), abd pain (19%),
weight loss (9%), diarrhea (3%); gr 3 nausea (9%); and gr 4 nausea (6%).
Late gr �3 GI toxicity was seen in 9%. Mean QOL score 4 wks post-SBRT
was similar to baseline (p�0.38). At 6 mos there was a trend towards
improved QOL (p�0.07). Conclusions: Fractionated SBRT with GEM
achieves high rates of LPFS and tumor response. Minimal grade �3 acute
and late toxicity was observed. SBRT is more likely to benefit patients with
Ca-19-9 �90. A combination of SBRT with more aggressive chemotherapy
may further improve outcomes.
Gastrointestinal (Noncolorectal) Cancer
249s
4044 General Poster Session (Board #41C), Mon, 8:00 AM-12:00 PM
Evaluation of predictive factors for thromboembolic events in patients with
advanced pancreatic cancer: Evaluation of the CONKO-004 (PROSPECT)
study cohort. Presenting Author: Uwe Pelzer, Universitätsmedizin Berlin,
Charité Centrum für Tumormedizin, Berlin, Germany
Background: Patients (pts) with advanced pancreatic cancer (APC) often
suffer from symptomatic thromboembolic events (sVTE). The CONKO-004
trial showed that the low molecular weight heparin (LMWH) enoxaparin
reduces sVTE (p�0.05, number needed to treat: 12) without increasing the
rate of major bleeding when prophylactically applied. Our goal was to
identify predictive factors for sVTE in pts with APC undergoing first-line
chemotherapy. Methods: We analyzed the 152 (out of 312) pts randomized
in the observation group.SVTE incidence was 9.9%. To identify foremost
risk factors we used clinical parameters like performance status, stage,
grading, primary or recurrent, gender, age, body mass index, erythropoietin
stimulating agents (darbepoetin), as well as baseline laboraty parameters
such as creatinine, hemoglobin, WBC, platelets, INR, ptt, CEA, carboanhydrat
19-9, AST, ALT, AP and GGT. The multivariate logistic regression
model with forward stepwise selection process was used for this estimation.
With reference to a previously proposed scoring system (Khorana et al;
Blood 2008) we evaluated the score as well. Results: No single parameter
could be isolated demonstrating significant influence on the incidence of
sVTE in pts with APC. We verified the Kohrana scoring model with our
152/312 pts. Applying the score to our pts we didn’t discriminate pts
between the two high risks groups (Table). Conclusions: Predictive models
may help to identify cancer pts at high risk for sVTE to consider preventive
anticoagulation. Within a cancer entity at high risk for sVTE such as pts
with APC we did not succeed in the identification of single predictive
parameters.For pts with APC undergoing first line chemotherapy primary
prevention with LMWH should therefore be considered for the whole group
of pts for at least three months.
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