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

338s Gynecologic Cancer
5046 General Poster Session (Board #18F), Sun, 8:00 AM-12:00 PM
Neo-escape: Neoadjuvant extended sequential chemotherapy with adjuvant
postoperative treatment for epithelial nonmucinous advanced inoperable
peritoneal malignancy. Presenting Author: Christopher John Poole,
University Hospital Coventry and Warwickshire NHS Trust, Coventry,
United Kingdom
Background: Neo-Escape was designed to exploit fully the modest non-cross
resistance of carboplatin (CBDCA) and paclitaxel (ptx) in an extended
sequential regimen, with dose-dense ptx, and address feasibility of combining
gemcitabine (gem) with either CBDCA or ptx. Methods: A randomised
phase II trial in patients (pts) with untreated (FIGO stage 3C/4) inoperable
ovarian, fallopian, or primary peritoneal carcinoma to assess feasibility of
two regimens of sequential neoadjuvant-then-adjuvant chemotherapy (CT);
(a) CBDCA AUC 2.5 and gem 1000mg/m2 repeated days 1 and8q3wksx
6 cycles, then ptx 175mg/m2 q 2 wks x 6 cycles (CG-P) or (b) CBDCA AUC 6
q 3 wks x 6 cycles, then ptx 175mg/m2 and gem 2000mg/m2 q2wksx6
cycles (C-PG). All pts were considered for delayed 1o debulking surgery
after neoadjuvant CT. The 1o feasibility outcome was % pts completing 12
cycles of CT. Using Fleming’s single stage procedure 44 patients on each
arm were needed to test null hypothesis of feasibility �60% with 5%
1-sided significance level and 90% power. 2o outcomes included safety,
PFS and ORR. Pts were stratified by serum albumin, stage and tumor
differentiation. Results: 75 pts were recruited Sept 2007 - May 2011 (28
CG-P; 47 C-PG), median age 62 yr (range 21-75). Recruitment to CG-P
closed early due to futility. 52% had albumin �35g/L, 68% FIGO stage 3C
and 80% poorly differentiated tumors. 64% on CG-P and 55% on C-PG had
debulking surgery as planned and a further 4% on CG-P and 13% on C-GP
after completion of all CT. For CG-P 35% achieved 0cm, 35% �1cm and
30% � 1cm residuum; for C-GP 34% 0cm, 13% �1cm and 34% �1cm,
19% TBC. 14/28 pts on CG-P completed all 12 cycles (feasibility 50%;
95% CI 31-67%); 37/47 pts on C-PG (feasibility 79% (95% CI 64-88).
Main reason for early discontinuation was toxicity on CG-P and disease
progression on C-PG. Similar proportions of pts on each arm had dose
reductions (68%) or delays (86% on CG-P; 89% on C-PG), mainly for
toxicity. 82% of pts experienced grade 3/4 toxicity on CG-P; 72% on C-PG.
Median PFS for CG-P is 14.3 mths (95% CI 11.6-15.7mths) and 13.0
mths (95% CI 11.5-15.4mths) for C-PG. Conclusions: CG-P was not
feasible at these doses using pre-specified criteria, but C-PG is feasible.
5048 General Poster Session (Board #18H), Sun, 8:00 AM-12:00 PM
NKTR-102 in patients with platinum-resistant ovarian cancer (PROC):
Modeling CA125 response and its correlation with tumor response.
Presenting Author: Yen Lin Chia, Nektar Therapeutics, San Francisco, CA
Background: NKTR-102 is a unique topoisomerase 1 inhibitor that provides
continuous exposure to SN38. In heavily pretreated pts with PROC (median
of 3 prior therapies; 27 pts were platinum refractory), 145 mg/m2 NKTR-102 given q14d or q21d demonstrated significant anti-tumor
activity (JCO 28:7s, 5013). We present a PK/PD model for CA125 kinetics
that can be used to project GCIG response as an aide to selecting dose and
schedule. Methods: Data from 55 pts with PROC and elevated CA125
(median baseline � 515 U/mL) were fit with a PK/PD model developed to
correlate CA125 dynamics with SN38 conc-time profiles predicted from
individual pt dosing history: d[CA125]/dt � Kin*exp(beta*t)*(1-[SN38]/
(IC50�[SN38]))-Kout*[CA125]. Results: CA125 profiles were well described
by the model, with a population mean SN38 IC50 of 1.1 ng/mL.
Typical min and max SN38 conc during treatment were 1.5 and 3 ng/mL
for q14d and 0.9 and 2.4 ng/mL for q21d, indicating that both schedules
resulted in SN38 exposure near the IC50. The half-life of CA125 decline
was 6.4 days, similar to literature values. 46 of 55 pts had pre- and
post-treatment tumor measurements for correlation of CA125 response and
tumor size. Overall best response by GCIG and RECIST correlated in 57% of
pts. 33% of pts with GCIG response showed declines in tumor size, albeit
insufficient to classify as RECIST response. 72% of pts with GCIG SD
showed at least SD by RECIST. CA125 vs time was simulated for 1000 pts
receiving 145 mg/m2 NKTR-102 q14d or q21d, to allow comparison of
CA125 and GCIG response between schedules (see table). The % pts per
GCIG response was comparable between schedules, supporting use of the
better-tolerated q21d regimen. Conclusions: The PK/PD model described
CA125 profiles well, providing a tool to predict drug response from SN38
PK data. Close correlation of CA125 with tumor size is consistent with
historical use of CA125 as a surrogate marker. Predicted CA125 profiles for
NKTR-102 q14d or q21d were similar, suggesting that the better-tolerated
q21d schedule will produce results consistent with those from Ph 2.
Model-predicted % pts by response.
CR PR SD PD
q14d 19 23 44 14
q21d 16 22 46 16
5047 General Poster Session (Board #18G), Sun, 8:00 AM-12:00 PM
Changes of serum glycome in patients suffering from ovarian cancer.
Presenting Author: Veronique Blanchard, Institute of Laboratory Medicine,
Clinical Chemistry and Pathobiochemistry, Charité Berlin, Berlin, Germany
Background: Protein glycosylation plays an important role in many biological
processes. Most human serum proteins, with the exception of albumin,
are glycosylated. Glycosylation is known to be altered with development of
diseases such as cancer. In the case of ovarian cancer, tumor markers
among them CA-125 that are clinically used are known to have poor
specificity. In addition, they fail to detect the disease at an early stage.
Therefore, better biomarkers are needed. The aim of the present research
work is to identify new potential glycan biomarkers by analyzing the serum
N-glycome of patients suffering from ovarian cancer Methods: Serum was
collected from 67 patients as well as from 33 healthy age-matching
women. N-glycans were released from 10 ul serum by PNGase F digestion,
permethylated and subsequently analyzed by means of MALDI-TOF mass
spectrometry. The SPSS software was used for the statistical analysis.
Results: The N-glycome of patients was found to have more fucosylated
structures, especially in tri- and tetraantennary sialylated glycans. The PCA
analysis indicates that there are significant differences between the
glycome of ovarian cancer patients in all stages of the disease and the
glycome of healthy controls. We identified 14 potential structures that were
divided in two categories, one of monofucosylated structures with high
antennarity (sensitivity 94%, specificity 97%) and one containing highmannose
structures and an asialylated structures (sensitivity 97%, specificity
97%). Conclusions: Our study is the first trial to identify major
differences between ovarian cancer sera and control sera, which could
potentially be used in the future as biomarkers.
5049 General Poster Session (Board #19A), Sun, 8:00 AM-12:00 PM
Longitudinal health-related quality of life assessment: Implications for
prognosis in ovarian cancer. Presenting Author: Donald Peter Braun,
Cancer Treatment Centers of America, Zion, IL
Background: Several studies in the oncology literature have demonstrated
the prognostic value of baseline quality of life (QoL). However, there is little
to no information on the prognostic effects of changes in QoL during
treatment. We investigated whether changes in QoL could predict survival
in ovarian cancer patients treated with an integrative model of care.
Methods: We evaluated 137 ovarian cancer patients treated at our institution
between Jan 2001 and Dec 2009 who were available for a minimum
follow-up of 3 months. QoL was evaluated at baseline and after 3 months of
treatment using EORTC-QLQ-C30. The QLQ-C30 incorporates a global
scale, 5 function scales and 8 symptom scales. Patient survival was defined
as the time between date of first patient visit and date of death from any
cause/date of last contact. Cox regression was performed to evaluate the
prognostic significance of baseline and changes in QoL scores after
adjusting for age, treatment history and stage at diagnosis. Results: Mean
age at diagnosis was 51.1 years. 28 patients were newly diagnosed while
109 were previously treated. Stage at diagnosis was I, 16; II, 15; III, 72; IV,
28; and 6 indeterminate. Median overall survival was 33.5 months (95%
CI: 11.5-55.6 months). Baseline QoL scale predictive of survival upon
multivariate analysis was nausea/vomiting (p�0.04). Associations between
changes in QoL and survival were observed for global function, appetite loss
and constipation. Every 10-point increase (improvement) in global function
from baseline to 3 months was associated with a 10% decreased risk of
death (HR�0.90; 95% CI�0.81 to 0.99, p�0.03). The corresponding
HRs for 10-point increase (deterioration) in appetite loss and constipation
scales were 1.20 (1.06 to 1.35; p�0.005) and 1.13 (1.02, 1.24;
p�0.02) respectively. Conclusions: This exploratory study provides some
preliminary evidence to indicate that ovarian cancer patients whose QoL
improves within 3 months of treatment have a significantly increased
survival time compared to those who fail to demonstrate improvement.
These findings might be used in clinical practice to systematically address
QoL-related problems of ovarian cancer patients throughout their treatment
course.
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