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

346s Gynecologic Cancer
5078 General Poster Session (Board #22F), Sun, 8:00 AM-12:00 PM
BRCA mutations and outcome in epithelial ovarian cancer (EOC): Experience
in ethnically diverse groups. Presenting Author: Tamar Safra, Department
of Oncology, Tel Aviv Sourasky Medical Center, Sackler School of
Medicine, Tel-Aviv University, Tel Aviv, Israel
Background: EOC patients with BRCA mutations have been reported to have
better prognosis than non-hereditary (NH) matched cases, an advantage
shown especially in the Ashkenazi-Jewish (AJ) population. We have
analyzed our experience in our ethnically diverse patient cohort from NYC,
Israel and Italy. Methods: A retrospective chart review of patients diagnosed
with Stage IC-IV EOC between 1995-2008 at the NYU Cancer Institute, Tel
Aviv Sourasky MC and Padova Clinical Cancer Centers. Out of �700
patients, 183 were tested for BRCA mutations and evaluated. Results:
Median age was 55.5 (range 31–83 years). Out of 183, 86 are carriers of
BRCA1/2 mutations and 97 tested negative, 67 and 19 are carriers of
BRCA1 and BRCA2 mutation respectively. Carrier frequency in EOC
population is 46% (45/97) in AJ’s and 48% (41/86) in non-AJ’s. AJ
patients had the following BRCA1 mutations: 185delAG (29), 5382insC
(5), unknown (UK) (2) and BRCA2 mutations: 6174delT (8), UK (1).
Non-AJ’s were divided by ethnicities into non-AJ, Caucasian, African-
American, Hispanic, Middle Eastern or unknown. Non-AJ Jewish patients
had BRCA1 mutations in 185delAG (7) and BRCA2 in 6174delT (1), UK
(1). Non-Jewish Caucasians exhibited the widest variation of mutation
types, with the following BRCA1 sites: 185delAG, K1702X (5223A�T),
E1373X, 3829delT, 185delAT, IVS11�1G�A, 5385insC,
5083del19�stop1670, 1720delAF�stop536, 1806C/T�Igu536Ter, del
ex1a-2, cod1486ex14:4575delAstop1504, 5563G7A;Trp1815stop,
5181delGTT(Val1688del) and UK and the following BRCA2 sites: 6174delT
(2), 5301insA (1), 802delAT (1), cod2960ex22:9106C/t (1), cod68ex3:
432delAstop79 (1), 7408A/T;Arg2394stop (1). One African-American
patient with BRCA1 at 1294del40, 1 Hispanic BRCA1 at 185delAG. OS
was significantly prolonged for BRCA carriers at 93.6 months versus 63.2
months [95% CI: 44.5-91.7] (p�0.0016) for NH. Conclusions: Our data
reports a wide variety of BRCA mutations in an ethnically diverse EOC
population and confirms that BRCA mutations carriers have a better
prognosis with a longer median survival compared to NH population. A
larger cohort might manifest prognostic differences between the different
types of mutations.
5080 General Poster Session (Board #22H), Sun, 8:00 AM-12:00 PM
A matched pair analysis of intra- and postoperative catumaxomab in
patients with ovarian cancer from a multicenter, single-arm phase II trial
versus a consecutive single-center collective of ovarian cancer patients
without immunotherapy. Presenting Author: Klaus Pietzner, Charite University
Medicine of Berlin, Berlin, Germany
Background: Advanced ovarian cancer is still connected to high mortality
rates due to intraperitoneal tumor cells that survive radical cytoreductive
surgery as well as adjuvant chemotherapy. These persistent tumor cells
need to be targeted in order to improve survival. Catumaxomab has
demonstrated the ability to kill EpCAM-positive intraperitoneal tumor cells
of ovarian cancer patients in studies aiming to controll malignant ascites in
the recurrent setting. This analysis was conducted to investigate the
efficacy of intraperitoneal catumaxomab at the timepoint of primary
cytoreductive surgery and postoperative period, prior to standard adjuvant
chemotherapy. Methods: Ovarian cancer patients undergoing radical surgery
received one intraoperative (10 �g) followed by four subsequent
intraperitoneal (i.p.) dosages (10, 20, 50 and 150 �g) of catumaxomab on
days 7, 10, 13, and 16, respectively. Because of the single arm design of
the study, the patients treated with catumaxomab were compared in a
matched pair analysis to consecutive patients with primary ovarian cancer
who received standard treatment without catumaxomab in a large center, in
order to compare survival. The two main prognostic factors of stage and
level of tumorreduction were chosen as matching criteria. Results: Of 58
patients screened, 41 were treated with catumaxomab and available for
survival evaluation. Median age was 57 years in the catumaxomab group
and 59 years in the matched-pair control group. The most comon histology
was the serous subtype with 70.7 % in the catumaxomab and 80.5 % of the
patients in the control group. The median for overall survival was reached
for the historical consecutive matched-pair control collective, but is not yet
reached for the catumaxomab group. However, 3-year survival data were
available for both groups and showed survival of 85.4% (35) in the
catumaxomab group and 63.4% (26) in the matched-pair control group
(p-value: 0.041; HR 2.073) Conclusions: There seems to be a trend to
beneficial 3-year survival in the catumaxomab group, suggesting that a
phase III trial is warranted.
5079 General Poster Session (Board #22G), Sun, 8:00 AM-12:00 PM
Serum IGFBP4 levels in combination with miliary disease: A candidate
predictor of ovarian cancer progression-free survival. Presenting Author:
Samantha Cohen, Mt Sinai School of Medicine, New York, NY
Background: Insulin-like growth factor binding protein, IGFBP4, was shown
to be highly expressed across all stages of epithelial ovarian cancer (EOC)
and serum levels are elevated in EOC. Moreover, IGFBP4 levels are ~3x
greater in women with malignant pelvic masses. We investigated whether
ascites volume and the presence of miliary disease in combination with
serum levels of IGFBP4 are independent predictors of survival. Methods: A
prospective and retrospective analysis was performed. Patients were
enrolled at the time of cytoreductive surgery. Ascites volume was either
absent, �500 cc (low), or �� 500 cc (high), and the presence of miliary
disease was recorded. The IGFBP4 cutoff was 1064.5 ug/ml based upon
previous results. The Kaplan-Meier product limit method was used to
estimate PFS probabilities. The Cox proportional hazards model was used
to estimate hazard ratios (HR) and corresponding 95% CI. Results: 57
cases were included in the analysis of ascites volume and miliary disease.
Cytoreductive outcomes were complete gross resection (44.8%), optimal
(��1cm residual disease; 44.8%), and suboptimal ( �1cm residual
disease; 10.3%). Histologic subtypes: papillary serous (n�35; 61.4%),
mucinous (n�15; 26.3%), endometrioid (n�4; 7.0%), and clear cell
(n�3; 5.3%). Stage distribution was 21.1% I/II, and 78.9% III/IV. PFS
was unaffected by ascites volume (p�0.341) or miliary disease. Among
this cohort, 29 had IGFBP4 levels available for a separate analysis.
Patients with high IGFBP4 and miliary disease were 5.5 times as likely to
recur compared with patients with miliary disease and low IGFBP4
(HR�5.55 [0.77, 39.82]), and the statistical significance was borderline
(p�0.088). No statistically significant differences were detected between
rates of recurrence among patients with high and low IGFBP4 values in
combination with ascites volume. Conclusions: These exploratory studies
suggest that patients with high IGFBP4 serum levels and miliary disease
were � 5 times as likely to recur compared to women with miliary disease
and low IGFBP4 levels. Future studies examining these variables using a
larger population and examining the biologic basis of this relationship are
planned.
5081 General Poster Session (Board #23A), Sun, 8:00 AM-12:00 PM
Progression-free survival (PFS) as a surrogate end point for overall survival
(OS) in first-line treatment of advanced epithelial ovarian cancer (EOC).
Presenting Author: Katrin Marie Sjoquist, NHMRC Clinical Trials Centre,
University of Sydney, Sydney, Australia
Background: The duration and cost of clinical trials of first-line chemotherapy
in advanced EOC could be reduced if a surrogate endpoint were
used in place of OS. The consensus of the Gynecological Cancer Intergroup
was that PFS is the preferred primary end point for these trials due to
potential confounding of post-progression therapy on OS. We performed a
systematic review to assess the extent to which treatment effect on PFS is
predictive of OS in this patient population. Methods: Randomised trials of
first-line chemotherapy comparing platinum containing regimens in advanced
EOC were identified; trials with non-platinum backbone, maintenance
strategies or biological containing therapies were excluded. Summary
data (hazard ratios (HR), median PFS and OS and the ratios of medians
between treatment arms) were extracted. Weighted least-square (WLS) R2 by trial sample size derived using linear regression was used to report
correlation. Results: 15 eligible trials with 19 treatment comparisons were
identified comprising a total of 16,598 patients. There was a good
correlation between treatment effect on PFS and OS (correlation of HR: r,
0.88, WLS R2 , 0.71; correlation of ratios of medians: r, 0.84, WLS R2 ,
0.72). Good correlation between treatment effect on PFS and OS was also
observed in various prognostic subgroups (Table). Conclusions: In clinical
trials of first-line platinum based chemotherapy without biological agents
in advanced EOC, treatment effect on PFS and OS is highly correlated. PFS
could be considered as a primary end point when evaluating future first line
strategies in advanced EOC.
Prognostic factors across trials
low vs. high split at median Correlation for HR (r) WLS R 2
Stage IV (16%) 0.94 vs. 0.75 0.79 vs. 0.57
Optimal debulking (62.6%) 0.86 vs. 0.95 0.69 vs. 0.83
Age (59 years) 0.93 vs. 0.86 0.77 vs. 0.66
ECOG performance status ECOG 2 and 3 (10.1%) 0.95 vs. 0.89 0.81 vs. 0.76
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