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

58s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
1036 General Poster Session (Board #19C), Sat, 8:00 AM-12:00 PM
A phase II study of foretinib in triple-negative, recurrent/metastatic breast
cancer: NCIC CTG trial IND.197 (NCT01147484). Presenting Author:
Daniel Rayson, QEII Health Sciences Centre, Halifax, NS, Canada
Background: Met, a receptor tyrosine kinase, is preferentially expressed in
basal-like compared to luminal breast cancer. In murine models, overexpression
of the oncogenic Met receptor transgene induces tumors with human
basal gene expression characteristics supporting Met inhibition as a
treatment strategy for triple negative (TN) breast cancer. Foretinib is an oral
multi-kinase inhibitor of Met, RON, AXL, TIE-2 and VEGF receptors with
anti-tumor activity in advanced HCC and papillary renal cell cancer.
Methods: Patients (pts) with TN breast cancer and 0-1 prior regimens for
metastatic disease received daily foretinib 60 mg po in a 2-stage single arm
trial. Primary endpoints were objective response and early progression rates
per RECIST 1.1. Tumor samples were centrally reviewed to confirm
ER/PR/HER2 status and for correlative studies including Met, PTEN and
EGFR expression. Stage 1 accrual required 23 response-evaluable Met
unselected patients with accrual continuing if �/� 1 response or � 17
early progressions (PD �� 8 weeks on study) were observed. Results:
Accrual is 29 pts to date; 24 are eligible, 22 evaluable for toxicity and 15
for response. Median age is 56 y (43-81), ECOG PS 0-1 in 23/24. Grade 3
laboratory adverse events were: lymphopenia (9%), elevations in ALT (5%),
GGT (5%) and INR (5%). Treatment-related non-hematologic toxicities
included (all/grade 3-4) fatigue (64%/5%), nausea (55%/5%), diarrhea
(41%/5%), hypertension (32%/14%), vomiting (27%/0%), anorexia (23%/
5%) and rash (14%/0%). Three SAEs possibly related to foretinib included;
asymptomatic pulmonary embolism, reversible CHF and pleural effusion
with QTc prolongation. One PR (7%), 8 early PD (53%) and 6 SD (40%)
have been observed to date with median SD duration of 5.4 months (range
2.7-5.5). Preliminary correlative results (IHC): 5/8 (62.5%) evaluable Met
positive cases had SD and 4/5 (80%) Met negative cases had PD as best
response. Met IHC was negative in the pt with PR. Conclusions: Foretinib
shows preliminary evidence of activity and tolerability in metastatic, TN
breast cancer. Stage 2 of accrual will include 15 pts with pre-treatment
biopsies of metastases and circulating tumor cell collection.
1038 General Poster Session (Board #19E), Sat, 8:00 AM-12:00 PM
Single institution experience with neoadjuvant chemotherapy for metaplastic
breast cancer (MBC). Presenting Author: Anna Kaminsky, University of
Pittsburgh Medical Center (UPMC), Pittsburgh, PA
Background: Metaplastic breast carcinoma (MBC) is a rare subtype that
accounts for �1% of all breast carcinomas. MBC is frequently triple
negative and neoadjuvant chemotherapy (NAC) is often used in triple
negative breast cancer (TNBC). The objective of this analysis is to ascertain
response rates of MBC to NAC as compared to non-metaplastic TNBC.
Methods: We searched the Magee Women’s Cancer Center of UPMC
IRB-approved neo-adjuvant treatment database which contains outcome
data on 594 patients treated from 2004-2010. 116 patients with triple
negative breast cancer (ER /PR negative or ER /PR weakly positive (H score
of 10 or less) and HER2 negative or indeterminate (HER2 1� or 2�
without amplification by FISH)), were identified. Nine of these TNBCs had
metaplastic subtype and 2 groups were analyzed: metaplastic breast
carcinoma (MBC) (N� 9) and non-metaplastic breast carcinoma (NMBC)
(N � 107). Tumor volume reduction (TVR), pathologic complete response
(pCR), recurrence and mortality were compared in both groups. Results:
Mean follow up in MBC group was 43 months and no patients were lost to
follow up. Mean tumor size on presentation in MBC group was 4.47 cm
while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and
43/107 NMBC cases (p � 0.0253). 6/9 patients had mastectomy, 2/9 had
breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet.
Average TVR was 28% in MBC cases compared to 74% in NMBCs when
cases with pCR were included (p � 0.0001) and 56% when cases with pCR
were excluded (p � 0.0202). Follow up on 9 MBC cases revealed 1
recurrence and subsequent death (11%). Follow up on 64 NMBC patients
who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them
subsequently died (28%).Follow up on 43 NMBC cases that achieved pCR
revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was
characterized by larger size at baseline as compared to NMBC. There were
no pCR’s seen in MBC, but some MBC did achieve response that allowed for
breast conservation. Although the average tumor volume reduction was
significantly less in MBC compared to NMBC, the NMBC that failed to
achieve pCR fared much worse than MBC who did not achieve pCR.
Therefore, the triple negative paradox is likely not applicable to MBC.
1037 General Poster Session (Board #19D), Sat, 8:00 AM-12:00 PM
Comprehensive investigation of adverse event (AE)-related costs in patients
with metastatic breast cancer (MBC) treated with first- and second-line
chemotherapies. Presenting Author: Sara A. Hurvitz, UCLA, Los Angeles,
CA
Background: MBC is incurable and managed with ongoing therapy. This
study examined the incremental costs of chemotherapy-associated AEs in
MBC. Methods: The PharMetrics Integrated Database (2000-2010) was
used to identify MBC pts treated either 1st or 2nd line with a taxane (T)
(paclitaxel or docetaxel) or capecitabine (C)-based regimen for �30 days
(defined as a treatment episode (TE)). Incremental costs attributable to
AEs were assessed by comparing costs incurred during TEs with and
without AEs. AEs were identified using medical claims with a diagnosis for
�1 event of interest (e.g., infections, fatigue, anemia, neutropenia). Pt
characteristics were balanced between comparison groups (with and w/o
AEs) using inverse probability weighting method. Incremental monthly
costs due to AEs were estimated during the TEs and included the following
cost components: inpt (IP), outpt (OP), emergency room (ER), other
medical service, pharmacy costs (chemotherapy and other drugs), and total
healthcare costs. Statistical comparisons were conducted using Wilcoxon
tests. Results: 3,222 women (mean age�57) received aTorCas1stor
2nd-line therapy for MBC. Of the 2,678 1st-line pts, 69.7% received T and
30.3% with C; average monthly total costs ranged from $9,159 to
$10,298. AEs were commonly seen in pts treated with 1st-line T and C
(94.6% and 83.7%). On average, the total monthly incremental cost
associated with AEs was 38% higher ($3,547) for T and 9% higher ($854)
for C. IP and other drug costs accounted for a majority of these costs. Of
1,084 2nd-line pts, 66% received T and 34% C, with average monthly total
costs ranging from $5,950 to $12,979. 94.4% of T pts and 84% of C pts in
the 2nd-line had an AE. The average total monthly incremental cost
associated with AEs for T was $5,320 and $4,933 for C (69.5% and
82.9% higher vs pts w/o AEs). Pharmacy costs accounted for a majority of
increased costs seen in pts with AEs treated with T; IP and OP accounted
for a majority of these costs in pts treated with C. Conclusions: This is the 1st study assessing costs associated with AEs for tx of mBC. AEs are associated
with a substantial economic burden that is mainly explained by increased
IP, OP, and pharmacy costs.
1039 General Poster Session (Board #19F), Sat, 8:00 AM-12:00 PM
Association between vitamin D deficiency and breast cancer histology: A
retrospective database review. Presenting Author: Ranjana S. Bhargava,
University of Maryland Marlene and Stewart Greenebaum Cancer Center,
Baltimore, MD
Background: Vitamin D (Vit D) deficiency has been shown to be associated
with a higher risk of developing breast cancer. Inverse association has also
been shown between vit D level and tumor size. However, the association
between vit D deficiency and breast cancer histology remains unclear.
Preclinical data has suggested that vit D plays an essential role in the
terminal differentiation of breast cells. Thus, we hypothesize that vit D
deficiency would be associated with estrogen receptor-negative tumors,
particularly triple-negative breast cancers (TNBC) which are associated
with aggressive clinical course. Methods: We conducted a retrospective
database review to obtain information including age, race, tumor histology,
size, stage, and vit D levels in newly diagnosed breast cancer patients at
University of Maryland Greenebaum Cancer Center. Results: 150 patients
presented between July 2008 and August 2011 were included in this
analysis. Average age at diagnosis was 57 (range 30-87), and 56% of
patients were African American. Overall, 80% of the patients were vit D
deficient at diagnosis, with levels � 30 ng/ml. African-American patients
were more likely to be severely vit D deficient with levels � 10 ng/ml
compared to Caucasians (33% vs. 7.5%, p� 0.0002). Patients with TNBC
were more likely to be vit D deficient at diagnosis compared to hormone
receptor-positive patients (93% vs. 76%, p �0.015). These patients also
had the lowest mean (18) and median (16) of vit D levels compared to all
other patients. This difference is also statistically significant in multivariate
analysis when adjusted for age, race, and stage (OR 3.96; p�0.04).
Regardless of the ER/PR status, Her 2 negative patients were more vit D
deficient compared to Her 2 positive patients (86% vs. 61%, p�0.001).
Unlike previous studies, no correlation was seen between tumor size and vit
D levels. Furthermore, there is also no association between stage, nodal
involvement, or Ki67 and vit D level. Conclusions: Vit D deficiency is
common among patients with newly-diagnosed breast cancer, particularly
African American patients. Patients with TNBC have a significantly higher
likelihood of being vit D deficient than patients with other histological
subtypes.
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