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

342s Gynecologic Cancer
5062^ General Poster Session (Board #20F), Sun, 8:00 AM-12:00 PM
Phase I safety study of farletuzumab, carboplatin, and pegylated liposomal
doxorubicin (PLD) in patients with platinum-sensitive epithelial ovarian
cancer (EOC). Presenting Author: Kenneth H. Kim, University of Alabama
at Birmingham, Birmingham, AL
Background: Farletuzumab (FAR) is a humanized monoclonal antibody that
binds to folate receptor-�, a target which is largely absent in normal
epithelium and over-expressed in EOC. A phase I and a phase II study
indicate potential utility of FAR in combination with carboplatin/paclitaxel
in recurrent platinum sensitive EOC. This study assessed safety and
efficacy of FAR in combination with PLD/carboplatin, which has been
demonstrated to have greater efficacy than carboplatin/paclitaxel in women
with platinum-sensitive EOC. Methods: A multicenter, single-arm study
enrolled 15 patients with platinum-sensitive EOC in first or second relapse
defined by either CA-125 or RECIST. The primary endpoint is to assess
safety of FAR plus PLD/carboplatin in this population. Patients were
treated with weekly FAR 2.5 mg/kg plus carboplatin AUC 4-5 and PLD 30
mg/m2 every 4 weeks for 6 cycles, followed by maintenance treatment with
single agent FAR until disease progression. Initial dosing of weekly 2.5
mg/kg was later amended to 7.5 mg/kg every 3 weeks. Results: 13 of 15
patients completed 6 cycles of combination therapy; one received a total of
12 cycles of chemotherapy. Two patients progressed during combination
therapy: one received 3 cycles, the other 5 cycles. The median number of
subsequent single agent maintenance cycles was 8 (range 0-13). No grade
4 toxicities were observed. Of 20 grade 3 toxicities in 14 patients, 3 (1
fatigue; 2 small bowel obstructions in the same patient) were deemed by
the investigator to be possibly related to FAR. These events were seen
during the combination phase and were deemed by the investigator to be
also possibly related to chemotherapy. All patients demonstrated clinical
benefit: 1 complete response, 10 partial response and 4 stable disease. 7
patients have come off study, all for disease progression; a median PFS of
11 months was noted. 8 patients remain on study. Conclusions: These
preliminary data indicate that the safety profile of FAR in combination with
carboplatin and PLD is consistent with that historically recorded for
carboplatin and PLD alone. Complete safety profile will be assessed; PK
data and final results will be presented.
5064 General Poster Session (Board #20H), Sun, 8:00 AM-12:00 PM
Application of an ointment with high radical protection factor as a
prevention strategy against PPE. Presenting Author: Franziska Kluschke,
Center of Applied Cutaneous Physiology (CCP), Department of Dermatology,
Charité-Universitätsmedizin Berlin, Berlin, Germany
Background: Pegylated liposomal doxorubicin has proved to be highly
efficient in the treatment of various tumors. Depending on the application
protocol, up to 80% of patients develop palmar-plantar erythrodysesthesia
(PPE). So far, a prevention strategy is still unknown. Recently, it was shown
that parts of the chemotherapeutics were excreted with the sweat onto the
skin surface, spreading there homogeneously and penetrating into the
stratum corneum. The formation of free radicals in the tissue results in
PPE. The aim of the study was to investigate if a topically applied ointment
containing antioxidants with high radical protection factor (RPF) can be a
PPE prevention strategy. Methods: 20 patients with ovarian carcinoma, who
had been treated with pegylated liposomal doxorubicin (40 mg/m2 ), were
investigated. They applied the ointment at least twice daily, 2 days before
and during 3 cycles of chemotherapy. Their skin condition was examined by
a trained dermatologist. Results: From 20 patients enrolled in the study,
only 12 (60%) met the conditions by applying the cream at least twice daily
in the palmar and plantar regions. These patients did not develop PPE. One
patient died in the 2nd cycle of therapy. 7 patients (35%) did not follow the
ointment application protocol for various reasons; 6 of them developed PPE
and resumed ointment application thereafter. As a result, PPE disappeared
or was strongly reduced in these patients so that chemotherapy could be
continued. Due to the small group of patients, the fact that PPE was not
induced in patients who had applied the ointment regularly can be
generalized only restrictedly. Far more interesting are the findings in those
patients, who had stopped ointment application during chemotherapy and
developed PPE, which disappeared after they resumed applying the
ointment. The regression or distinct reduction of PPE after re-application of
the ointment clearly proves the efficacy of this strategy. Conclusions: The
topical application of an ointment containing antioxidants with high radical
protection factor (RPF) could be an efficient strategy against the development
of PPE during chemotherapy.
5063 General Poster Session (Board #20G), Sun, 8:00 AM-12:00 PM
Factors associated with an increased risk of recurrence in women with
ovarian granulosa cell tumors. Presenting Author: Anuj Suri, The University
of North Carolina Hospitals, Division of Gynecologic Oncology, Chapel Hill,
NC
Background: There is emerging data in different malignancies, including
gynecologic cancers, demonstrating factors independent of a patient’s
tumor characteristics, which are associated with an increased risk of cancer
recurrence. The goal of this study is to determine demographic and
prognostic factors affecting recurrence of disease (RD) in women with
ovarian granulosa cell tumors (GCT). Methods: A dual-institution retrospective
analysis of patients diagnosed with GCT between 1995 and 2010.
Demographics including age, race, BMI, stage, diabetes (DM), adjuvant
treatment, and progression free survival (PFS) were extracted. Hazard
ratios for recurrence were estimated by univariate and multivariate Cox
regression models Results: One hundred nine women identified with a
median age of 50 (range 12-87). Fifty-six (57.1%) were Caucasian, 32
(32.7%) African American, and 10 (10.2%) were other. Median BMI was
29 (range 12-57). Twenty-one patients had DM. The majority of women
had stage I disease (89.0%), 7 (6.4%) had stage II/III disease, and 5 were
unstaged. In univariate analysis, DM showed the strongest association with
recurrence (HR 3.56, 95% CI: 1.57-8.11). Non-white race was also
associated with higher risk of RD, though the association was not
statistically significant (HR 1.74, 95% CI: 0.78-3.87). The association
between DM and RD was also found in multivariate analysis controlling for
all factors including non-white race and BMI (HR 2.99, 95% CI: 1.11-
8.08). Only 19 (17%) patients received adjuvant chemotherapy consisting
of one of two different adjuvant chemotherapy regimens bleomycin,
etoposide, and cisplatin or paclitaxel and carboplatin, however there was no
difference in outcome based on chemotherapy regimen (p�0.24).
Conclusions: This is the largest study analyzing factors associated with risk
of recurrence in women with ovarian GCT. Studies have demonstrated
higher morbidity among diabetic patients with breast and colon cancer and
this may be modifiable with metformin. Our results emphasize that
diabetes is one of the strongest predictors of recurrent disease in patients
with ovarian GCT. Further studies are necessary to evaluate the effect of
other factors such as adjuvant chemotherapy.
5065 General Poster Session (Board #21A), Sun, 8:00 AM-12:00 PM
A phase I, dose escalation trial to assess the safety and biological activity of
recombinant human interleukin-18 (SB-485232) in combination with
pegylated liposomal doxorubicin in platinum-resistant recurrent ovarian
cancer. Presenting Author: Fiona Simpkins, University of Miami Miller
School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL
Background: SB-485232, a recombinant human form of interleukin-18
(IL-18), is being studied as a novel cytokine for tumor immunotherapy.
IL-18 has been shown to increase the anti-tumor activity of doxorubicin in
other cancer mouse models. Methods: This multi-center study enrolled 16
patients (pts), and evaluated four cycles (28 days each) of standard
pegylated liposomal doxorubicin (PLD) (40 mg/m2 day 1) in combination
with increasing doses of IL-18 (1, 3, 10, 30, and 100 mg/kg) on days 2 and
9 of each cycle witha1yrfollow-up to further evaluate safety and efficacy.
Results: Of the 16 pts, 10 (63%) completed study treatment and 6 (37%)
did not because of disease progression (5 pts) and PLD hypersensitivity (1
pt). Thirteen (82%) were platinum resistant/refractory having received a
median of � 3 prior lines of therapy. SB-485232 up to 100 mg/kg in
combination with PLD had an acceptable safety profile. All 16 pts
experienced at least 1 AE including chills (81%), nausea (75%), anemia
(63%), fatigue (56%), hyperglycemia, and pyrexia (50% each). Eight of 16
pts had Grade 3 AEs including anemia (19%), and 6% each for abdominal
pain, asthenia, dehydration, PLD hypersensitivity, edema, fatigue, hyperglycemia,
hyperkalemia, jaundice, pain, nausea, vomiting, and pyelonephritis.
There were no grade 4/5 AEs. Four subjects experienced 10 non-fatal
SAEs with 3 related to study drug: anemia, PLD hypersensitivity, and
cytokine release syndrome. Maximal SB-485232 biological activity, assessed
by peripheral blood NK and T cell markers, was observed at
10mg/kg-100mg/kg. This drug combination resulted in a 6% partial
response rate (RR) and a 38% stable disease rate using RECIST 1.0.
Median (95% CI) time of progression-free survival (PFS) was 4.50 (3.52,--)
months. Conclusions: The SB-485232/PLD combination was tolerable with
minimal toxicity. These preliminary efficacy data are comparable to the
historical RR and PFS observed with PLD monotherapy in platinumresistant
ovarian cancer. However, given the small sample size, this
combination warrants further investigation.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.