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

4075 General Poster Session (Board #45B), Mon, 8:00 AM-12:00 PM
Post-recurrence survival in patients with previously resected esophageal
adenocarcinoma (EAC). Presenting Author: Mark Lewis, Mayo Clinic
College of Medicine, Rochester, MN
Background: EAC recurrence after surgery with curative intent is believed to
carry a uniformly dismal prognosis that may discourage further therapy. To
date, the post-recurrence survival of patients has not been examined in
EAC. Our aim was to examine site of recurrence in relation to outcome in
EAC patients after surgery. Methods: Among EAC patients (N � 796)
rendered margin-free at surgery performed at Mayo Clinic, most were T3-4
and lymph node (LN)-positive; none received neoadjuvant therapy. The
patient subset who had documented disease recurrence (N � 401) formed
the current study population. Cox models were used to examine overall
survival (OS) post-recurrence. Results: Among patients with recurrence,
median time to recurrence (TTR) was 11 months. Site of recurrence
included loco-regional (regional LNs, esophagogastric, anastomosis), chest,
abdomen, or distant sites in 97 (27%), 144 (40%), 181 (50%), and 88
(24%) patients, respectively. Most recurrences (66%) were limited to one
site. Chest-involved recurrence was significantly associated with improved
OS (hazard ratio [HR] 0.78, P � .047), even after adjusting for TTR,
number of recurrence sites, tumor pathology, and palliative chemotherapy.
This result was confirmed when multivariate analysis was restricted to
patients who had only 1 recurrence site (Table) or who had biopsy-proven
recurrence (P � .080). In separate models, abdomen-involved (HR � 1.3,
P � .016) or bone-involved (HR � 1.6, P� .008) recurrences were
independently associated with worse OS. Conclusions: Chest-involved
recurrence of EAC independently predicts for improved survival, whereas
abdominal and bony sites of recurrence predict for worse outcome. Primary
tumor grade and node number were durable prognosticators after recurrence.
These novel data provide useful prognostic information and have the
potential to influence clinical decision-making.
Predictors for post-recurrence survival in a multivariate model.
HRa p
Chest-only, yes v no 0.69b .021
Grade, 4 v 1-3 1.36 .027
Malignant LN, per additionalnode 1.06 .003
Palliative chemo, yes v no 0.57 �.0001
TTR, > v < 11 mos 0.99 .265
a Adjusted for all variables. b 95% confidence interval 0.50 - 0.95.
4077 General Poster Session (Board #45D), Mon, 8:00 AM-12:00 PM
Phase II trial of tesetaxel, an oral taxane, as second-line therapy for patients
with advanced gastroesophageal cancer. Presenting Author: Mary Frances
Mulcahy, Northwestern University, Chicago, IL
Background: Tesetaxel is a novel, orally administered taxane. It is not a
substrate for P-glycoprotein, and preclinical data suggest tesetaxel has
potent antitumor activity that exceeds standard taxanes in human tumor
xenografts while causing substantially less neuropathy. Tesetaxel is not
associated with hypersensitivity, thus eliminating the need for premedication
and extended observation. A prior study showed an overall major
response rate (ORR) of 20% with tesetaxel used as 2nd-line therapy in
patients (pts) with advanced gastric cancer. We previously showed that
“flat” (i.e., non weight-based) dosing with tesetaxel was associated with
excessive variability; therefore, we amended the final trial design to
evaluate whether we could extend the prior observations in a confirmatory
Phase 2 trial using the MTD. Methods: Eligibility included: adenocarcinoma
of stomach/GE junction; 1 prior fluoropyrimidine-platinum regimen; ECOG
PS 0-1; and adequate organ function. Tesetaxel was administered orally
once every 3 weeks starting at 27 mg/m 2 escalated to 35 mg mg/m2 pending tolerance. ORR was the primary endpoint; estimated overall
survival (OS) was secondary. Results: To date, 24 pts -- from a final target of
27 – have been enrolled (10 men, 14 women; median age, 58 yrs [range,
26-81]). Preliminary ORR in 15 evaluable cases to date are shown in the
table below. At this time, only 4 pts have died and median survival is too
early to estimate. Grade 3-4 adverse events have included neutropenia
(27%), anemia, fatigue (13% each), and anorexia (7%). One pt (7%)
experienced Grade 3 peripheral neuropathy. There have been no episodes
of febrile neutropenia. Conclusions: Oral tesetaxel administered once every
3 weeks is active against gastric cancer in the 2nd-line setting. The
observed 20% ORR confirms earlier data and appears at least equivalent to
docetaxel (ORR� 5%-19%), as reported in 4 prior studies in this
population. Tesetaxel was well tolerated and was not been associated with
hypersensitivity. We expect to present final ORR and estimated OS from
this trial.
Response N � 24
Evaluable (n) 15
Partial 3 (20%)
Stable disease 3
Progression 9
Too early 10
Response duration, mos 1.5�,3�,4�
Gastrointestinal (Noncolorectal) Cancer
257s
4076 General Poster Session (Board #45C), Mon, 8:00 AM-12:00 PM
Prognostic impact of FHIT, APC, and HER2 status in resected gastric
cancer: A clinical-biological risk stratification model. Presenting Author:
Emilio Bria, Department of Pathology and Diagnostics, University of
Verona, Verona, Italy
Background: The dismal prognosis of gastric cancer prompts for the
identification of factors predictive of survival/response to treatment. The
potential prognostic value of 11 molecular markers was investigated in a
retrospective series of 208 resected gastric cancers. Methods: Molecular/
clinicopathological data were correlated to cancer-specific/overall survival
(CSS/OS) using a Cox model. Molecular data were: microsatellite instability,
CDX2, APC, ß-catenin, E-Cadherin, FHIT, P53, p21, HER-2 (IHC/
FISH), TOPO2A amplification (FISH) e PIK3CA mutation (exons 9/20).
ROC analysis provided optimal cut-offs and model validation. A logistic
equation with regression analysis coefficients was constructed to estimate
individual patients’ probability (IPP) of death. Internal cross-validation
(100 simulations, 80% of the dataset) was accomplished. Multivariate
model Ratios served to derive a prognostic continuous score to identify risk
classes. Results: 208 patients were studied (median follow-up 16 months,
range 1-155). Multivariate analysis selected 8 independent CSS predictors:
sex (HR 1.53, p�0.04), stage (HR 5.40, p�0.0001), R (HR 2.69,
p�0.0001), localization (HR 1.64, p�0.008), LN (HR 1.55, p�0.02),
APC (HR 1.91, p�0.001), FHIT (HR 1.54, p�0.05) and HER-2 (HR 1.92,
p�0.08). Independent OS predictors were: sex, age, stage, R, localization,
LN, APC and HER-2. Cross-validation analysis confirmed APC, FHIT and
HER-2 as the biological variables displaying significant correlation with
CSS (replication: 98%, 51%, 31%). The multivariate model predicted a
2-yr IPP of cancer-death/death with a prognostic accuracy of 0.87 (SE
0.02)/0.91 (SE 0.02). A 2-class risk stratification model was developed
with the ROC generated cut-off prognostic score (AUC 0.87, SE 0.03;
Sensitivity 85.3%, Specificity 78.9%); see table below. This 2-class model
has a prognostic performance for CSS/OS of 0.82 (SE 0.03)/0.81 (SE
0.02). Conclusions: FHIT, APC and HER-2 represent powerful prognostic
factors for resected GC and may complement clinical parameters to
accurately predict individual patient risk.
Low risk (score < 6) High risk (score > 6) p value
CSS 82.5% 16.4% �0.0001
OS 79.7% 15.6% �0.0001
4078 General Poster Session (Board #45E), Mon, 8:00 AM-12:00 PM
Outcome of 58 trimodality-eligible esophagogastric cancer (EC) patients
who achieved clinical complete response (cCR) after preoperative chemoradiation
but then declined surgery. Presenting Author: Takashi Taketa,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: For patients with EC who can withstand surgery, the preferred
therapy is trimodality. However, after achieving a cCR (defined as postchemoradiation
negative endoscopic biopsy for cancer and post-chemoradiation
physiologic FDG uptake by PET), some patients are tempted to
decline surgery. Literature is sparse on the outcome of such patients.
Methods: Between 2002 and 2011, we identified 621 trimodality-eligible
EC patients in our prospective database. All patients had to be trimodalityelgible
and must have received preoperative chemoradiation and completed
preoperative staging that included a repeat endoscopic biopsy and
PET-CT prior to surgery among other routine tests. Results: Of 621
trimodality-eligible patients identified, 58 patients declined surgery after
completing chemoradiation. All patients had a cCR. The median age was
69 (range, 47-85). Male (84.5%) and Caucasian (91.4%) were dominant.
Baseline stage was II (44.8%) or III (51.7%) and histology was adenocarcinoma
(67.2%) or squamous cell carcinoma (29.3%). 40 patients remain
alive at a median follow up of 50.4 months (95% CI, 38.6-62.1). 5-year OS
and relapse-free survival were 56.7�9.0% and 32.9�7.7%. Of 12
patients with local recurrence during surveillance, 11 had salvage resection.
Conclusions: Although, the outcome of EC patients with cCR who
declined surgery appears reasonable, in the absence of a validated
prediction/prognosis model, only trimodality therapy must be encouraged
for trimodality-eligible patients. Supported by UT M. D. Anderson Cancer
Center grants and generous donors.
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