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

48s Breast Cancer—HER2/ER
TPS667 General Poster Session (Board #18A), Sat, 8:00 AM-12:00 PM
ASTER 70s: Benefit of adjuvant chemotherapy for estrogen receptorpositive
HER2-negative breast cancer in women over 70 according to
genomic grade—A French GERICO/UCBG UNICANCER multicenter phase
III trial. Presenting Author: Etienne Brain, Hôpital René Huguenin/Institut
Curie, Saint-Cloud, France
Background: The benefit of adjuvant chemotherapy (CT) is highly controversial
for elderly breast cancer (BC) women presenting with an oestrogen
receptor-positive (ER�) HER2-negative (HER2-) phenotype. Conversely to
hormonal treatment (HT) that remains the cornerstone of adjuvant treatment
for such luminal tumours, CT may severely decompensate comorbidities
and alter quality of life in elderly patients. As disappointing as it is in
drug development, elderly have been constantly excluded from trials
evaluating new modern prognosis classifiers. This prospective multicentre
trial funded by a French national grant (PHRC 2011) is the first phase III
trial to investigate the impact on overall survival (OS) of adjuvant CT in
elderly ER� HER2- BC patients selected with a modern prognosis classifier
and taking into account competing risks for mortality (EudraCT 2011-
004744-22). Methods: Following surgery, 2,000 women 70� with ER�
HER2- BC (any pT/pN), will have a genomic grade (GG, derived from frozen
MapQuantDx, Ipsogen) centrally assessed on formalin-fixed paraffinembedded
samples. Only those with a high GG (estimation~700) will be
randomized between HT alone vs CT followed by HT. CT regimen is left to
the choice of investigators amongst 3 regimen of same duration [4 q3w
cycles, docetaxel�cyclophosphamide, doxorubicin or non pegylated liposomal
doxorubicin (Myocet)�cyclophosphamide, all with G-CSF], as well
as HT (aromatase inhibitor�tamoxifen). Those with low GG or not included
for other reasons (estimation~1,300) will be followed as an observational
parallel cohort with HT alone. Sample size is based on 4-year OS as primary
endpoint (87.5 vs 80%), bilateral ��0.05, ��0.20 and HR� 0.60.
Secondary endpoints include assessment of competing risks for mortality,
cost-effectiveness and Q-TWiST analysis, geriatric items (e.g. Lee’s 4-year
mortality score and G8 screening tool), acceptability, quality of life
(QLQ-C30 and specific elderly scale ELD15), and translational research on
ageing/prognostic biomarkers and pharmacogenetic. The trial has been just
opened to inclusion in February 2012.
TPS669 General Poster Session (Board #18C), Sat, 8:00 AM-12:00 PM
Aromatase inhibitors, arthralgias, and exercise in breast cancer survivors.
Presenting Author: Melinda Irwin, Yale University, New Haven, CT
Background: A substantial number of breast cancer survivors who are taking
aromatase inhibitors (AIs) complain of side effects including arthralgias.
Given the efficacy of AIs, it is essential that we identify approaches to
mitigate arthralgias. We are conducting an NCI-funded trial is to examine
the impact of a year-long exercise intervention in 180 breast cancer
survivors taking an AI and experiencing at least mild arthralgias. Outcomes
include severity of arthralgias, endocrine-related quality of life, % body fat,
bone mass, and serum markers of inflammation. The purpose of this
abstract is to present preliminary recruitment and adherence results.
Methods: Women are being recruited via the Connecticut Tumor Registry
and Rapid Case Ascertainment Shared Resource of Yale Cancer Center into
the Hormones and Physical Exercise (HOPE) Study. Participants are
randomly assigned to exercise (n � 90) or usual care (n � 90). The exercise
intervention includes supervised resistance and unsupervised aerobic
exercise sessions over 12 months. Data are collected at baseline, 3-, 6-, 9
and 12-months. Results: Study recruitment began in April 2010 and will
continue through December 2012. As of January 1, 2012, we have
received 1605 names of potentially eligible women. Of these 1605, 777
women are waiting to be screened (e.g., letter mailed to patient or on hold
because recently diagnosed), 244 women could not be screened (e.g.,
unable to contact by phone), and 584 women have completed a telephone
screening. Of the 584 women screened, 24% were ineligible because of
discontinuing AIs because of arthralgias or chose not to take AIs primarily
because of this potential side effect; another 36% were ineligible for
various reasons; 24% were not interested; 11% were randomized (n � 65
women); and 5% are undergoing baseline visits (n � 29). On average,
women are 62 yrs old and have been taking an AI for 1.8 yrs. Twenty-three
women have completed the trial, with high exercise adherence rates
(attendance to supervised sessions � 82% ). Conclusions: A growing
number of women are choosing to not take AIs or are discontinuing AIs
because of side effects. Our study may prove beneficial for the growing
number of women diagnosed with hormone receptor-positive breast cancer
each year.
TPS668 General Poster Session (Board #18B), Sat, 8:00 AM-12:00 PM
MDV3100-08: A phase I open-label, dose-escalation study evaluating the
safety, tolerability, and pharmacokinetics of MDV3100 in women with
incurable breast cancer. Presenting Author: Anthony D. Elias, University of
Colorado Anschutz Medical Campus, Aurora, CO
Background: MDV3100 is a novel, orally administered small molecule that
directly binds the androgen receptor (AR) to potently inhibit AR-mediated
signaling via three mechanisms: inhibition of androgen binding to AR;
inhibition of AR nuclear translocation; and inhibition of nuclear AR
association with DNA. MDV3100 is not known to agonize AR signaling, can
be taken without prednisone, and demonstrated an overall survival benefit
in post-docetaxel prostate cancer at 160 mg/day. AR expression is observed
in ~70% of all breast cancer (BCa) regardless of histologic subtypes
(estrogen receptor [ER] positive, HER2�, and triple negative [TN] disease).
MDV3100 has demonstrated preclinical activity in AR�/TN and AR�/
ER� BCa and could be a potential therapeutic strategy in patients with
AR� BCa. Methods: This Phase 1 study has 2 stages: a standard 3�3
dose-escalation stage (S1), evaluating safety, tolerability, and pharmacokinetics
(PK) of MDV3100, starting at 80 mg MDV3100; and a doseexpansion
stage (S2), evaluating the recommended Phase 2 dose in ~15
women with AR� BCa. All patients must have received �2 chemotherapycontaining
regimens for their incurable BCa, or �3 anti-HER2 containing
regimens for their incurable HER2� BCa to be eligible; ER� patients must
be post-menopausal. In S1, patients will receive their assigned dose of
MDV3100 on Day 1, and PK samples will be collected through Day 8. Daily
dosing will begin on Day 8 and will continue until predefined discontinuation
criterion is met. Dose-limiting toxicities will be recorded through Day
35 and used to determine the Phase 2 dose. Extensive PK sampling is
performed on Days 1 and 50 with predose PK samples collected throughout.
In S2, patients with AR� BCa (defined as 10% or more tumor cells
with nuclear AR expression) will take daily MDV3100 at the recommended
Phase 2 dose; there is no single dose PK period. Tumor tissue submission is
mandatory in S2. Safety and tolerability will be documented by frequent
assessments of adverse events, vital signs, and laboratory assessments.
Tumor assessments occur at 2 months then approximately every 3 months
thereafter. Enrollment of 27 subjects is anticipated.
TPS670 General Poster Session (Board #18D), Sat, 8:00 AM-12:00 PM
Denosumab versus placebo as adjuvant treatment for women with earlystage
breast cancer who are at high risk of disease recurrence (D-CARE): An
international, randomized, double-blind, placebo-controlled phase III clinical
trial. Presenting Author: Paul Edward Goss, Massachusetts General
Hospital Cancer Center, Boston, MA
Background: Bone is a common site of distant recurrence in women with
early-stage breast cancer, and represents approximately 40% of all first
recurrences. Tumor cells in bone release growth factors and cytokines that
stimulate osteoclast-mediated bone resorption through the RANK ligand
(RANKL) pathway. In preclinical studies, RANKL inhibition significantly
delays skeletal tumor formation, reduces skeletal tumor burden, and
prolongs survival of tumor-bearing mice. Denosumab is a fully human
monoclonal antibody that binds to RANKL with high affinity and specificity.
It is approved for the prevention of skeletal-related events in patients with
established bone metastases from a variety of solid tumors. The purpose of
the D-CARE trial is to evaluate the ability of denosumab to prolong bone
metastasis-free survival (BMFS) and disease-free survival (DFS) in the
adjuvant breast cancer setting. Methods: Approximately 4,500 women with
stage II or III breast cancer, at high risk for recurrence and with known
hormone and HER-2 receptor status, are eligible. Standard-of-care adjuvant
or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone
or in combination must be planned. Exclusion criteria include: a prior
history of breast cancer (except DCIS or LCIS) or distant metastasis, oral
bisphosphonate (BP) use within 1 year of randomization or any intravenous
BP use. Patients are randomized 1:1 to receive denosumab 120 mg or
placebo subcutaneously monthly for 6 months, then every 3 months for a
total of 5 years of treatment. All patients receive vitamin D (� 400 IU) and
calcium (� 500 mg) supplements. Primary endpoint of this event-driven
trial is BMFS. Secondary endpoints include DFS and overall survival.
Safety, quality of life assessments, breast density, and biomarkers are
additional endpoints. The trial, sponsored by Amgen Inc. and registered
with the ClinicalTrials.gov identifier NCT01077154, began enrolling patients
in June 2010 and is expected to complete in October 2016. Paul
Goss and Dianne Finkelstein supported in part by the Avon Foundation New
York.
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