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

10092 General Poster Session (Board #53E), Sun, 8:00 AM-12:00 PM
Explored prognostic factors for survival in patients with advanced GIST
treated with standard dose imatinib (IM): Results from the BFR14 phase III
trial of the French Sarcoma Group. Presenting Author: David Pérol, Centre
Léon Berard, Lyon, France
Background: Factors predicting progression free survival (PFS) and overall
survival (OS) of patients (pts) with advanced GIST treated with 400 mg
daily dose IM included in the BFR14 study with a median follow up of 54
months (CI95%:47-61) was investigated evaluating added prognostic
factors. Methods: 434 pts were included in this prospective multicenter
trial from June 2002 to July 2009. After 1, 3 and 5 yrs of IM 400mg/day,
pts free from progression were randomly offered to continue or interrupt (I
arm) IM. Prognostic factors for overall survival were investigated in the
entire cohort (randomized and not randomized pts) included in the BFR14.
Survival was defined from the date of inclusion to the date of death for OS or
to the first occurrence of disease progression under imatinib or death for
PFS. A multivariate cox model including statistical significant baseline
characteristics tested in univariate were included in a backward procedure
d to identify independent prognostic factors for PFS then OS. Results: As of
January 2012, there were 285 progressions (65%) and 161 deaths (37%).
The median PFS of the entire cohort was 29 months (CI95%: 24-33) and
the 4 and 5-yrs PFS were 31% and 24% respectively. A low tumour volume
at inclusion, PS (0), sex (female), CD34 positivity on tumor cells were the
four independent prognostic factors of a higher PFS. The 5-yrs OS was 54%
(CI95%: 48-60). A higher OS was independently predicted by gender
(female), PS (0), platelets count (�400 giga/L) and CD34 expression on
GIST cells. Median PFS and OS were slightly superior in this more recent
series as compared to B2222 consistently with the improved outcome of
patients with low tumor volume. Conclusions: OS and PFS are predicted by
gender, PS and CD34 expression in this large series of pts treated with
standard dose IM. The biological significance of CD34 expression on tumor
cells has to be explored in GIST.
10094 General Poster Session (Board #53G), Sun, 8:00 AM-12:00 PM
Characteristics of gastrointestinal stromal tumor (GIST) patients receiving
short-term versus long-term imatinib (IM) adjuvant therapy: A chart review
analysis. Presenting Author: Annie Guerin, Analysis Group, Inc., Boston, MA
Background: In clinical practice, significant variability is seen in duration of
adjuvant IM use. The objective of this study is to compare characteristics of GIST
pts receiving adjuvant IM for a short (6-12 months) vs extended period (�24
months) to better understand factors that may influence treatment (trt) duration
decisions. Methods: Physician prescribing patterns and clinical information on
adult pts with primary resectable Kit positive GIST initiating IM �84 days
post-surgery was collected from 248 U.S. oncologists using online data
collection forms. In addition to physicians’ perception of short- vs long-term use,
pts’ risk assessment, trt, demographics, and comorbidities were collected for
246 short-term and 395 long-term IM pts. Characteristics were compared using
Wilcoxon and Chi-square tests. Results: While pts were similar in age [59.0 vs.
58.1, P �.23], ethnicity, and region of residence, the short-term group included
fewer males (57.7% vs 69.6%, P �.01) and had a higher prevalence of
cardiovascular (11.4% vs 5.8%, P � .01) and ischemic heart diseases (5.3% vs
1.5%, P�.01). Differences were also observed in indicators of pre-treatment risk
profile (tumor size, location, and rupture during surgery, mitotic count, and
Miettinen score) (Table). Findings were consistent with main reasons reported by
physicians for prescribing adjuvant IM over longer duration; in addition to pt risk
profile (76.6%), tolerability (70.6%), younger pts (59.7%), safety (39.1%), trt
response (29.8%), and economic reasons (26.2%) were other reasons impacting
trt decisions. Conclusions: Pt risk is an important factor in physicians’ decisions
to prescribe adjuvant IM for extended duration. However, age, tolerability, and
comorbidities, also play an important role.
Long-term Short-term
Tumor characteristics
Size (mean � SD)
Rupture during surgery, %
8.2 � 7.0 7.2 � 7.6 *
Yes 2.5 5.7 *
No 91.9 92.3
Unknown
Location, %
5.6 2.0 *
Stomach 53.9 44.3 *
Small intestine 29.6 27.6
Rectum 1.3 2.0
Other 15.2 26.0 *
Miettinen risk (mean � SD)
Mitotic rate (/HPF; %)
0.4 � 0.3 0.3 � 0.3 *
< 5 9.6 16.7 *
5 30.9 33.3
6–10 33.7 31.3
>10 17.7 11.8 *
N/A
* Significant at 5% level.
8.1 6.9
Sarcoma
653s
10093 General Poster Session (Board #53F), Sun, 8:00 AM-12:00 PM
The role of surgical cytoreduction before imatinib therapy in patients with
advanced GIST. Presenting Author: Hojung An, Division of Medical
Oncology, Asan Medical Center, Seoul, South Korea
Background: Despite dramatic improvement of survival with introduction of
imatinib mesylate, resistance to imatinib eventually develops in most of
patients with advanced gastrointestinal stromal tumor (GIST). It is well
known that baseline tumor size is an important factor related to imatinib
resistance. We hypothesize that decreasing tumor size by surgery before
starting imatinib may delay the emergence of resistance and improve
prognosis in patients with advanced GIST. Methods: From 2001 to 2010,
102 patients with initially metastatic GIST and 147 patients with recurrent
GIST were enrolled in this analysis. Patients with local relapse only were
excluded because they were potentially curable by surgery alone. Patients
were categorized into two groups according to the extent of cytoreduction;
i.e., patients whose initial tumor bulk reduced �75% surgically before
starting imatinib (group A) and the others (group B). Results: Among total
249 patients, 62 patients received initial surgery. 35 (14%) patients
whose tumor bulk reduced � 75% were categorized into group A, and the
remaining 214 (86%) were in group B. In group A, the median age was
younger; more patients were initially metastatic; peritoneal metastases
were more frequent; but liver metastases were less. The total tumor size was
significantly reduced from median 122 mm before cytoreduction to 0 mm
after on CT scans in group A. With a median follow-up of 42.7 months,
progression-free survival (PFS) tended to be better in group A than in group
B in univariate analysis (HR�0.60; 95% CI, 0.36-1.02; p�0.061), but
PFS was not statistically different between the two groups in multivariate
analysis (p�0.488). Meanwhile, absence of KIT exon 11 mutation
(p�0.007), baseline total tumor size � 150mm (p�0.043), and granulocyte
count � 5000/mm3 (p�0.009) remained independent poor prognostic
factors. Conclusions: Despite marked decrease of total tumor size, the
outcomes were not significantly improved in patients receiving initial
cytoreduction more than 75% of baseline tumor bulk before starting
imatinib. These results suggest that initial cytoreduction does not have
beneficial role in advanced GIST, so imatinib should be still the first
treatment of choice in this population.
10095 General Poster Session (Board #53H), Sun, 8:00 AM-12:00 PM
Effect of five years of imatinib on cure for patients with advanced GIST:
Updated survival results from the prospective randomized phase III BFR14
trial. Presenting Author: François Bertucci, Institut Paoli-Calmettes, Marseille,
France
Background: We previously demonstrated that interruption of imatinib (IM)
after 1, 3, and 5 yrs in responding patients (pts) with advanced GIST is
associated with rapid relapse but reintroduction of IM allowed tumor
control in almost all pts. Here, we examined the outcome of patients
randomized in the interruption arm (I arm), and notably the characteristics
of those not yet progressing. Methods: This prospective multicenter BFR14
study was initiated in June 2002 and closed for inclusion in July 2009.
Seventy-one non-progressing patients were randomized in the I arm after 1
(N�32), 3 (N�25) and 5 years (N�14) of IM 400 mg/day. IM (same dose)
was reintroduced in case of progressive disease (PD). Results: The median
follow-up (FU) from randomization was 74, 48 and 22 months for pts
randomized at 1, 3 and 5 yrs of IM treatment respectively. Updated survival
data (January 2012) are summarized in the table. Out of the 3 pts not
progressing in the I arm at 1 yr, 1 pt had refused to stop IM and 1 pt had a
localized GIST with small residual disease at inclusion. Out of the 3 pts not
progressing in the I arm at 3 yrs, 1 pt had refused to stop IM and 2 pts were
included after complete resection of both primary tumor and metastases
with a small residual disease. The FU of pts randomized at 5 yrs was short
but out of the 5 non progressive pts, 2 are considered in PD on functional
imaging (January 2012), 2 had a locally advanced GIST subsequently
operated during IM and before randomization, and 1 had no target lesion at
inclusion (resection of synchronous metastases). Conclusions: All but one
pts with residual masses under IM and randomized in the I arm have
relapsed. Six out of 7 patients not yet progressing in the I arm had reached
complete remission following surgery at inclusion or before randomization
(initial resection/debulking of metastases).
Parameter 1 yr 3 yrs 5 yrs
Randomized pts (I/continuous [C] arms) 58 (32/28) 50 (25/25) 27 (14/13)
Median PFS (months) I/C arms
7/29
9/49
13/not reached
(p)
p�0.0001
p�0.0001
p�0.017
2-y PFS (%) : I/C arms 13 [4-26] p / 11[2-27]p/80[58-91] 28[6-57]p/
62 [40-77]
92 [54-99]
No. pts non-progressive (I arm) (%) 3/32(9) 3/25(12) 5/14(35)
Post-randomization FU (months) 64, 73, 90 23, 46, 54 2, 3, 17, 18, 25
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