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

254s Gastrointestinal (Noncolorectal) Cancer
4063 General Poster Session (Board #43F), Mon, 8:00 AM-12:00 PM
Bisphosphonates and esophageal cancer: A RADAR report. Presenting
Author: Beatrice J. Edwards, Department of Medicine, Geriatrics Division,
Northwestern University Feinberg School of Medicine, Chicago, IL
Background: In 2009, the US Food and Drug Administration (FDA) reported
on 23 patients who had developed distal esophageal cancer, with alendronate
(ALN) within 2 years of initiation of therapy. Similarly, 31 cases of
esophageal cancer were reported from Europe and Japan. Esophagitis has
been associated with oral BPs. Erosive esophagitis and persistent mucosal
abnormalities have been noted with crystalline material (similar to ground
ALN). Our objective was to assess the FDA Adverse event reporting system
(FDA AERS) for a safety signal. Methods: The FDA Adverse Event Reporting
System (AERS) database was searched using terms related to esophageal
cancer combined with all drug names for bisphosphonates (search period:
1996-2010). Disproportionality ratios were calculated: Proportional reporting
ratio (PRR) and Empiric Bayes Geometric Mean (EBGM) determining
that the esophageal cancer cases were more common with bisphosphonates
than with other drugs in the database. Results: We identified 128
cases of bisphosphonate-associated esophageal cancer; 114 (89%) female
and 14 male (11%), mean age 72 � 12 yrs; the drugs included alendronate
(n�96, 75%), risedronate sodium (n�14, 11%), ibandronic acid (n�10,
7.8%), zoledronic acid (n�7, 5.4%) and pamidronate (n�1, 1%). Barrett’s
esophagus was listed in 3 cases of esophageal carcinoma. A
significant safety signal was found only for alendronate with a PRR� 6.4
(95% C.I. 5.29, 7.730; p�0.001), EBGM � 6.3 (95% C.I. 5.1, 7.6
p�0.001). Conclusions: Our analysis of FDA AERS identifies a larger
number of cases of esophageal cancer than previously described, and a
significant safety signal with alendronate use. Avoidance of oral bisphosphonates
in patients with Barrett’s esophagus, and persistent mucosal abnormalities
is recommended. Increased awareness and vigilance is needed for
patients receiving oral bisphosphonate therapy.
4065 General Poster Session (Board #43H), Mon, 8:00 AM-12:00 PM
Trastuzumab (TRA) in combination with different first-line chemotherapies
for treatment of HER2-positive metastatic gastric or gastroesophageal
junction cancer (MGC): Findings from the German noninterventional
observational study HerMES. Presenting Author: Susanna Hegewisch-
Becker, Internistische Praxisgemeinschaft Eppendorf, Hamburg, Germany
Background: The international phase III study ToGA has recently shown that
TRA is effective in prolonging survival in HER2-positive MGC. However, few
data are available for TRA as part of routine clinical practice. Methods: This
non-interventional observational study was conducted to evaluate the
efficacy, safety and feasibility of TRA in previously untreated pts with
HER2-positive MGC. Results: Between Apr 2010 and Jan 2012, data from
110 pts were collected. All pts were evaluable for safety. Baseline pt
characteristics were as follows: median age 63 yrs (range 29–88); gender
(male 70%; female 29%); ECOG PS (0: 25%; 1: 50%; 2: 15%; 3: 5%);
distant mets (91%); liver mets (54%), lymph node mets (35%); peritoneal
carcinomatosis (23%). The median duration of TRA treatment was 4.4
months (0–17.1). According to the schedule of chemotherapy TRA was
administered every 2–3 wks in a median dose of 4–6 mg/kg BW. Only 28%
of pts received TRA according to the label in combination with cisplatin and
5-FU or capecitabine. The remainder received: cisplatin, 5-FU and
leucovorin (17%); 5-FU, leucovorin, oxaliplatin and docetaxel (8%); 5-FU,
leucovorin and oxaliplatin (7%); capecitabine (6%); other combinations
(25%); TRA monotherapy (7%). Although most pts didn’t receive cisplatinbased
therapy, preliminary median progression-free survival was 6.8
months, thus comparable to the ToGA data. Most common adverse events
(AEs, all grades) were diarrhoea (7%), vomiting (5%) and nausea (5%).
Most common grade 3/4 AEs were vomiting (3%), nausea (2%) and fatigue
(2%). Health-related quality of life as assessed by EORTC QLQ-C30 and
QLQ-STO22 remained stable during observation time. An updated analysis
of approx. 200 pts will be presented at the meeting. Conclusions: TRA
combined with diverse chemotherapies is safe and effective in the routine
treatment of MGC. Cisplatin-free less toxic regimens are feasible and
equally effective. The results are in line with those from the ToGA trial and
suggest that treatment with TRA should be regarded as standard of care for
pts with HER2-positive MGC.
4064 General Poster Session (Board #43G), Mon, 8:00 AM-12:00 PM
Combined analysis of randomized controlled trial (RCT) and patientpreference
trial (PPT) evaluating second-line chemotherapy (SLC) in
advanced gastric cancer (AGC). Presenting Author: Soonil Lee, Dankook
University Hospital, Cheonan, South Korea
Background: While prolonged overall survival (OS) from SLC compared to
best supportive care (BSC) has recently been demonstrated for AGC (Park
et al, ASCO 2011), the prognosis of pretreated AGC remains poor. We
assessed whether patient preference, willing to participate onto RCT, or
other parameters contributed to this OS improvement. Methods: In the
phase III trial, pretreated AGC patients (n�372) were first offered RCT. If a
patient agreed to participate, randomly assigned 2:1 to SLC or BSC
(n�202). If refused RCT, but agreed to receive treatment of their
preference, they were offered SLC or BSC (PPT; n�170). OS of RCT
participants was compared to that of whole patient population according to
prognostic subgroups. In addition, analyses of OS unadjusted for multiple
comparisons were conducted across predefined subgroups. Results: Median
OS was 6.3 months among 254 patients treated with SLC and 3.3 months
among 118 patients treated with BSC (HR, 0.507; 95% CI, 0.405 to
0.637; one-sided p�0.001). Compared to the RCT patients, younger age
group, those with an ECOG performance status (PS) of 0, and with one prior
chemotherapy were under-represented in the PPT patients. OS was
comparable between RCT (5.0 months) and PPT (4.4 months) patients
even after controlling for major prognostic factors (log-rank p�0.322). The
OS benefit for SLC was preserved when analyzed according to baseline
parameters. Parameters that were associated significantly with a prolonged
OS included a PS of 0, the chemotherapy-free interval �3 months, and one
prior chemotherapy. When the analysis was adjusted for these three
parameters, patients who received SLC still had improved OS (HR, 0.554;
95% CI, 0.441 to 0.696; p�0.001). Conclusions: The 54% participation
rate obtained in the current study represents the best achievable rate for
this kind of phase III RCT involving BSC only arm. Even if we consider
differences in the baseline characteristics between RCT and PPT patients,
it is concluded that the RCT results can be generalized for the patient
population and provided additional evidence supporting the use of SLC in
patients with pretreated AGC.
4066 General Poster Session (Board #44A), Mon, 8:00 AM-12:00 PM
Does in-house availability of multidisciplinary teams increase survival in
upper GI cancer? Presenting Author: Christian Kersten, Center for Cancer
Treatment, Sørlandet Hospital Trust, Kristiansand, Norway
Background: Treatment of esophageal, gastric and pancreatic cancers (UGI)
is recommended to be discussed by a multidisciplinary team (MDT),
despite lack of evidence that this approach leads to increased survival. In
2001, a cancer centre with irradiation and chemotherapy facilities was
established in the Norwegian county of West Agder (WA), providing the
potential for local in-house MDT meetings. Our primary objective was to
evaluate the effect of the establishment of in-house MDT availability
(iMDTa) on survival in a cohort of UGI patients in WA. We compared
survival figures for WA with those of other Norwegian counties with
complete, less complete and without iMDTa. Methods: We defined “iMDTa”
as a single administrative institution with all departments on one campus,
serving the population of one county. We compared cause-specific survival
rates for 2000-04 and 2005-08 for UGI patients living in counties with
(MDT-Yes), without (MDT-No) and with a mix (MDT-mix) of iMDTa, with the
county of WA which had a change in iMDTa (MDT-Change) during the study
period. Crude survival was modelled with Kaplan-Meier method and Cox
regression analysis was used to adjust for age and region (sex and stage
distributions were similar in all counties). Results: We analyzed 12530 UGI
patients living in five Norwegian regions. Median age was 74 (17-98) yrs
and median follow-up was 5 (0-138) months. The regions with the highest
level of iMDTa achieved the largest increases in survival, compared to the
counties with limited or no iMDTa. Median overall survival for all UGI
patients in WA/MDT-Change increased from 129 to 300 days from 2000-8,
p�0.001. Compared to the county with MDT-Mix, the county with
MDT-Change reached a statistically significant reduction in the risk of
death (HR) for both esophageal (1.12- 0.60) and stomach cancers
(0.87-0.63), but not for pancreatic cancers (1.04-1.01). Conclusions: In
parallel with an increasing use of in-house MDT, we found a striking and
more than two-fold increase in survival in the Norwegian county of
WA/MDT-Change. This survival gain is partly explained by increased use of
chemotherapy. During the same time period, no increase in survival was
found in the MDT-No or MDT-Mix counties.
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