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

5106 General Poster Session (Board #28A), Sun, 8:00 AM-12:00 PM
ADXS11-001 immunotherapy targeting HPV-E7: Preliminary survival data
from a phase II study in Indian women with recurrent/refractory cervical
cancer. Presenting Author: Partha Basu, Chittaranjan National Cancer
Institute, Kolkata, India
Background: ADXS11-001 immunotherapy is a live attenuated Listeria
monocytogenes (Lm) bioengineered to secrete a HPV-16-E7 fusion protein
targeting HPV transformed cells. The Lm vector serves as its own adjuvant
and infects APC where it naturally cross presents, stimulating both MHC
class 1 and 2 pathways resulting in specific T-cell immunity to tumors.
Here we describe the preliminary survival data associated with ADXS11-
001 administration in Lm-LLO-E7-015, a randomized phase II study being
conducted in India in 110 patients with recurrent/refractory cervical cancer
who have been treated previously with chemotherapy, radiotherapy or both.
Methods: Patients are randomized to either 3 doses of ADXS11-001 at 1 x
109 CFU or 4 doses of ADXS11-001 at 1 x 109CFU with cisplatin
chemotherapy. Naprosyn and oral promethazine are given as premedications
and a course of ampicillin is given 72h after infusion thereby clearing
any residual vector. Patients receive CT scans at baseline and Days 84,
184, 273, 365 and 545. The primary endpoint is 12 month survival.
Results: As of January 26, 2012, 88 patients have received 200 doses of
ADXS11-001; with the percentage of patients alive at 6 months at 62%
(34/55); at 9 months at 41% (15/37) and at 12 months at 40% (6/15).
Tumor responses have been observed in both treatment arms with 3
complete responses (elimination of tumor burden) and 4 partial responses
(�30% reduction in tumor burden) by RECIST. One serious (Gr3) adverse
event and 77 mild-moderate (Gr 1-2) adverse events possibly related to
study treatment have been reported in 35% (31/88) of patients. The
non-serious adverse events consisted predominately of transient, noncumulative
flu-like symptoms associated with infusion that responded to
symptomatic treatment, or resolved on their own within hours of treatment.
Conclusions: This immunotherapy can be safely administered to patients
with advanced cancer alone and in combination with chemotherapy.
ADXS11-001 is well tolerated and presents a predictable and manageable
safety profile. Early signs of clinical benefit merit further investigation.
Updated findings will be presented at the meeting.
5108 General Poster Session (Board #28C), Sun, 8:00 AM-12:00 PM
Preoperative geriatric assessment (GA) and surgical outcomes in older
women with gynecological (gyn) cancer. Presenting Author: Daneng Li,
Memorial Sloan-Kettering Cancer Center, New York, NY
Background: GA can predict surgical outcomes in older patients (pts);
however, pre-surgical evaluation for older pts with gyn malignancies has not
been well-described. This study will determine the association between GA
variables with post-operative morbidity and mortality. Methods: Women
75yrs or older who had geriatric evaluation before any gyn surgery at
Memorial Sloan Kettering Cancer Center (MSKCC) between 1/2010-6/
2011 were identified. Pre-operative GA included: Mini-Cog Test (cognition),
fall history, medication list, nutritional status (weight loss �10lbs,
albumin), functional status (activities of daily living (ADL), instrumental
I-ADL), and Charlson comorbidity index. Outcomes included: delirium,
length of hospital stay (LOS), 30-day surgical adverse events (AE, grade
1-5, via prospective-MSKCC surgical database), 30-day hospital readmission
and 6-month mortality. Utilizing bivariate analyses, associations
between GA measures and post-operative outcomes were evaluated.
Results: 72 pts (median age 79yrs, range 75-92) with gyn cancer (54%
uterine, 36% ovarian/peritoneal/tubal, 10% cervical/vaginal/vulvar) had
gyn surgery. 34 pts (47%) had stage III/IV disease. 21pts (30%) had
secondary cancer history. Pt’s baseline GA measures: ADL-dependent
(13%), IADL-dependent (19%), weight loss (18%), fall history (18%), mini
cog score (median 4, range 0-5), Charlson score (median 2, range 0-9).
24pts (33%) had surgical AE; no significant association with age or GA.
Median LOS was 2 days (range 0-20); 11pts (15%) required 30-day
readmission. Delirium (p�0.01), nutrition (weight loss p�0.04, albumin
p�0.04), anemia (p�0.003) and high comorbidity index (p�0.013) were
associated with longer LOS. Six-month mortality was 8%; older age
(p�0.02), poor functional status (lower ADL and IADL, p�0.001 and
p�0.007), number of medications (p�0.05) and poor cognition (p�0.001)
were associated with shorter survival. Conclusions: Surgical morbidity is
common in older pts. Although AE’s were not associated with GA variables,
GA can detect high-risk features for longer LOS and shorter survival.
Further prospective studies with pre-operative GA and interventions are
warranted.
Gynecologic Cancer
353s
5107 General Poster Session (Board #28B), Sun, 8:00 AM-12:00 PM
Cervical cancer treatment for operable lesions in a low-resource contemporary
setting. Presenting Author: Caroline Dorothy Lynch, Indiana University,
Indianapolis, IN
Background: To compare HIV� and HIV- women with operable cervical
cancer in a low resource contemporary setting. Methods: A retrospective
study using well-matched controls from a Kenyan teaching and referral
hospital. Results: 183 women were treated for cervical cancer between
October 2007 and June 2011. The histologic subtype was squamous cell in
all but one case. At presentation, 28 had operable lesions (Stage IA1–
IIB1); 7 more received neoadjuvant chemotherapy prior to surgery. HIV
seroprevalence was 54% (18/33) among initial operative cases and 57%
among the neoadjuvant group (p�ns). Mean age was 42 (HIV�), and 43
(HIV-), (range 25-64). HIV- vs. HIV� cervical cancer patients (mean CD4
count 373, 50%�200) were detected by visual inspection with acetic acid
(VIA) (18% (2/11)vs 68% (15/22) p�.099), symptoms (27%(3/11) vs
14%(3/22) p�.43), or Pap smear (45% (5/11) vs .09% (2/22) p�.06),
respectively.HIV� patients (two Stage IB1, two Stage IB2) did not require
more downstaging than HIV- patients (two stage IIB, one stage IIIA) before
surgery (18% (4/22) vs 27% (3/11) p�.63). Surgical treatments were not
statistically different in either group and included radical hysterectomy(25),
total abdominal hysterectomy(2), cesarean hysterectomy(1),
and total vaginal hysterectomy(5). Postoperative complications included
fever, dehiscence, DVT, ileus, fistula, and infectious complications (chest,
urinary tract, wound). One HIV- patient suffered postoperative fever,
vesicovaginal fistula, and wound dehiscence (overall complications
.06%).Lymph node involvement was noted in 7 HIV� and 3 HIV- patients
who underwent full staging procedures (p�.004). Conclusions: In patients
with operable cervical cancer, HIV serostatus does not affect complication
rate or influence need for downstaging prior to surgery compared to a
well-matched control group. HIV� patients were not more likely to receive
neoadjuvant chemotherapy but were more likely to have positive lymph
nodes. VIA detected the majority of cervical cancers HIV� patients.
5109 General Poster Session (Board #29A), Sun, 8:00 AM-12:00 PM
Genome-wide association analysis in host characteristics of progression to
high-grade cervical intraepithelial neoplasia for women with human papilloma
virus infection and normal cytology. Presenting Author: Chyong-Huey
Lai, Gynecologic Cancer Research Center, Chang Gung Memorial Hospital
and Department of Obstetrics and Gynecology, Chang Gung University
College of Medicine, Taoyuan, Taiwan
Background: Although it is well accepted that persistent human papillomavirus
(HPV) is necessary for carcinogenesis of cervical neoplasms, the
molecular mechanism for progression is unclear. HPV testing is widely used
for cervical cancer screening. The hazard ratio of developing cervical
intraepithelial neoplasia grade 2 or more severe (CIN2�) in baseline
HPV-positive/normal cytology women is 30-50 fold as compared with
HPV-negative/normal cytoloy women. HPV positivity would cause substantial
anxiety. It is important to identify a prognostic profile for predicting
progression. Methods: We collected blood samples from women aged � 30
years in a population-based nested cohort study enrolling women with HPV
infection (n � 871) or HPV-negative (n � 902) with normal cytology in
2004-2009 for prospective follow-up. To identify the host genetic characteristics
associated with cervical carcinogenesis, a genome-wide association
study (analyzing 530,194 SNPs) was conducted in 23 cases who
developed CIN2� and 62 viral type- and age-matched controls who were
HPV-positive at baseline without developing CIN throughout the follow-up
period. Results: One SNP with significant P values (rs16969682; P�4.58 x
10-5 ,OR�5.9, 95% CI�2.52-13.96) located in SEC14-like 1 (SEC14L1)
gene localized to chromosome 17 was identified with association between
progression to CIN2� and controls without CIN throughout follow-up.
SEC14L1 belongs to the widely-expressed SEC14-superfamily. This superfamily
consists of � 500 members that are involved in biological functions
including membrane trafficking and phospolipid metabolism. Furthermore,
using T-cell based cDNA screening, SEC14L-1a is identified as a regulator
of HIV-1 replication. Conclusions: The potential role of SEC14L1 in
host-viral interaction will be further elucidated. Additional statistically
significant SNPs including rs16969682 will be validated on cases with
CIN2� (n � 250) and normal controls (normal cytology/HPV-negative at
baseline without acquisition of HPV or abnormal cytology/histology during
follow-up, n � 500).
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