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

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58s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy<br />

1036 General Poster Session (Board #19C), Sat, 8:00 AM-12:00 PM<br />

A phase II study <strong>of</strong> foretinib in triple-negative, recurrent/metastatic breast<br />

cancer: NCIC CTG trial IND.197 (NCT01147484). Presenting Author:<br />

Daniel Rayson, QEII Health Sciences Centre, Halifax, NS, Canada<br />

Background: Met, a receptor tyrosine kinase, is preferentially expressed in<br />

basal-like compared to luminal breast cancer. In murine models, overexpression<br />

<strong>of</strong> the oncogenic Met receptor transgene induces tumors with human<br />

basal gene expression characteristics supporting Met inhibition as a<br />

treatment strategy for triple negative (TN) breast cancer. Foretinib is an oral<br />

multi-kinase inhibitor <strong>of</strong> Met, RON, AXL, TIE-2 and VEGF receptors with<br />

anti-tumor activity in advanced HCC and papillary renal cell cancer.<br />

Methods: Patients (pts) with TN breast cancer and 0-1 prior regimens for<br />

metastatic disease received daily foretinib 60 mg po in a 2-stage single arm<br />

trial. Primary endpoints were objective response and early progression rates<br />

per RECIST 1.1. Tumor samples were centrally reviewed to confirm<br />

ER/PR/HER2 status and for correlative studies including Met, PTEN and<br />

EGFR expression. Stage 1 accrual required 23 response-evaluable Met<br />

unselected patients with accrual continuing if �/� 1 response or � 17<br />

early progressions (PD �� 8 weeks on study) were observed. Results:<br />

Accrual is 29 pts to date; 24 are eligible, 22 evaluable for toxicity and 15<br />

for response. Median age is 56 y (43-81), ECOG PS 0-1 in 23/24. Grade 3<br />

laboratory adverse events were: lymphopenia (9%), elevations in ALT (5%),<br />

GGT (5%) and INR (5%). Treatment-related non-hematologic toxicities<br />

included (all/grade 3-4) fatigue (64%/5%), nausea (55%/5%), diarrhea<br />

(41%/5%), hypertension (32%/14%), vomiting (27%/0%), anorexia (23%/<br />

5%) and rash (14%/0%). Three SAEs possibly related to foretinib included;<br />

asymptomatic pulmonary embolism, reversible CHF and pleural effusion<br />

with QTc prolongation. One PR (7%), 8 early PD (53%) and 6 SD (40%)<br />

have been observed to date with median SD duration <strong>of</strong> 5.4 months (range<br />

2.7-5.5). Preliminary correlative results (IHC): 5/8 (62.5%) evaluable Met<br />

positive cases had SD and 4/5 (80%) Met negative cases had PD as best<br />

response. Met IHC was negative in the pt with PR. Conclusions: Foretinib<br />

shows preliminary evidence <strong>of</strong> activity and tolerability in metastatic, TN<br />

breast cancer. Stage 2 <strong>of</strong> accrual will include 15 pts with pre-treatment<br />

biopsies <strong>of</strong> metastases and circulating tumor cell collection.<br />

1038 General Poster Session (Board #19E), Sat, 8:00 AM-12:00 PM<br />

Single institution experience with neoadjuvant chemotherapy for metaplastic<br />

breast cancer (MBC). Presenting Author: Anna Kaminsky, University <strong>of</strong><br />

Pittsburgh Medical Center (UPMC), Pittsburgh, PA<br />

Background: Metaplastic breast carcinoma (MBC) is a rare subtype that<br />

accounts for �1% <strong>of</strong> all breast carcinomas. MBC is frequently triple<br />

negative and neoadjuvant chemotherapy (NAC) is <strong>of</strong>ten used in triple<br />

negative breast cancer (TNBC). The objective <strong>of</strong> this analysis is to ascertain<br />

response rates <strong>of</strong> MBC to NAC as compared to non-metaplastic TNBC.<br />

Methods: We searched the Magee Women’s Cancer Center <strong>of</strong> UPMC<br />

IRB-approved neo-adjuvant treatment database which contains outcome<br />

data on 594 patients treated from 2004-2010. 116 patients with triple<br />

negative breast cancer (ER /PR negative or ER /PR weakly positive (H score<br />

<strong>of</strong> 10 or less) and HER2 negative or indeterminate (HER2 1� or 2�<br />

without amplification by FISH)), were identified. Nine <strong>of</strong> these TNBCs had<br />

metaplastic subtype and 2 groups were analyzed: metaplastic breast<br />

carcinoma (MBC) (N� 9) and non-metaplastic breast carcinoma (NMBC)<br />

(N � 107). Tumor volume reduction (TVR), pathologic complete response<br />

(pCR), recurrence and mortality were compared in both groups. Results:<br />

Mean follow up in MBC group was 43 months and no patients were lost to<br />

follow up. Mean tumor size on presentation in MBC group was 4.47 cm<br />

while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and<br />

43/107 NMBC cases (p � 0.0253). 6/9 patients had mastectomy, 2/9 had<br />

breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet.<br />

Average TVR was 28% in MBC cases compared to 74% in NMBCs when<br />

cases with pCR were included (p � 0.0001) and 56% when cases with pCR<br />

were excluded (p � 0.0202). Follow up on 9 MBC cases revealed 1<br />

recurrence and subsequent death (11%). Follow up on 64 NMBC patients<br />

who failed to achieve pCR revealed 22 recurrences (34%) and 18 <strong>of</strong> them<br />

subsequently died (28%).Follow up on 43 NMBC cases that achieved pCR<br />

revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was<br />

characterized by larger size at baseline as compared to NMBC. There were<br />

no pCR’s seen in MBC, but some MBC did achieve response that allowed for<br />

breast conservation. Although the average tumor volume reduction was<br />

significantly less in MBC compared to NMBC, the NMBC that failed to<br />

achieve pCR fared much worse than MBC who did not achieve pCR.<br />

Therefore, the triple negative paradox is likely not applicable to MBC.<br />

1037 General Poster Session (Board #19D), Sat, 8:00 AM-12:00 PM<br />

Comprehensive investigation <strong>of</strong> adverse event (AE)-related costs in patients<br />

with metastatic breast cancer (MBC) treated with first- and second-line<br />

chemotherapies. Presenting Author: Sara A. Hurvitz, UCLA, Los Angeles,<br />

CA<br />

Background: MBC is incurable and managed with ongoing therapy. This<br />

study examined the incremental costs <strong>of</strong> chemotherapy-associated AEs in<br />

MBC. Methods: The PharMetrics Integrated Database (2000-2010) was<br />

used to identify MBC pts treated either 1st or 2nd line with a taxane (T)<br />

(paclitaxel or docetaxel) or capecitabine (C)-based regimen for �30 days<br />

(defined as a treatment episode (TE)). Incremental costs attributable to<br />

AEs were assessed by comparing costs incurred during TEs with and<br />

without AEs. AEs were identified using medical claims with a diagnosis for<br />

�1 event <strong>of</strong> interest (e.g., infections, fatigue, anemia, neutropenia). Pt<br />

characteristics were balanced between comparison groups (with and w/o<br />

AEs) using inverse probability weighting method. Incremental monthly<br />

costs due to AEs were estimated during the TEs and included the following<br />

cost components: inpt (IP), outpt (OP), emergency room (ER), other<br />

medical service, pharmacy costs (chemotherapy and other drugs), and total<br />

healthcare costs. Statistical comparisons were conducted using Wilcoxon<br />

tests. Results: 3,222 women (mean age�57) received aTorCas1stor<br />

2nd-line therapy for MBC. Of the 2,678 1st-line pts, 69.7% received T and<br />

30.3% with C; average monthly total costs ranged from $9,159 to<br />

$10,298. AEs were commonly seen in pts treated with 1st-line T and C<br />

(94.6% and 83.7%). On average, the total monthly incremental cost<br />

associated with AEs was 38% higher ($3,547) for T and 9% higher ($854)<br />

for C. IP and other drug costs accounted for a majority <strong>of</strong> these costs. Of<br />

1,084 2nd-line pts, 66% received T and 34% C, with average monthly total<br />

costs ranging from $5,950 to $12,979. 94.4% <strong>of</strong> T pts and 84% <strong>of</strong> C pts in<br />

the 2nd-line had an AE. The average total monthly incremental cost<br />

associated with AEs for T was $5,320 and $4,933 for C (69.5% and<br />

82.9% higher vs pts w/o AEs). Pharmacy costs accounted for a majority <strong>of</strong><br />

increased costs seen in pts with AEs treated with T; IP and OP accounted<br />

for a majority <strong>of</strong> these costs in pts treated with C. Conclusions: This is the 1st study assessing costs associated with AEs for tx <strong>of</strong> mBC. AEs are associated<br />

with a substantial economic burden that is mainly explained by increased<br />

IP, OP, and pharmacy costs.<br />

1039 General Poster Session (Board #19F), Sat, 8:00 AM-12:00 PM<br />

Association between vitamin D deficiency and breast cancer histology: A<br />

retrospective database review. Presenting Author: Ranjana S. Bhargava,<br />

University <strong>of</strong> Maryland Marlene and Stewart Greenebaum Cancer Center,<br />

Baltimore, MD<br />

Background: Vitamin D (Vit D) deficiency has been shown to be associated<br />

with a higher risk <strong>of</strong> developing breast cancer. Inverse association has also<br />

been shown between vit D level and tumor size. However, the association<br />

between vit D deficiency and breast cancer histology remains unclear.<br />

Preclinical data has suggested that vit D plays an essential role in the<br />

terminal differentiation <strong>of</strong> breast cells. Thus, we hypothesize that vit D<br />

deficiency would be associated with estrogen receptor-negative tumors,<br />

particularly triple-negative breast cancers (TNBC) which are associated<br />

with aggressive clinical course. Methods: We conducted a retrospective<br />

database review to obtain information including age, race, tumor histology,<br />

size, stage, and vit D levels in newly diagnosed breast cancer patients at<br />

University <strong>of</strong> Maryland Greenebaum Cancer Center. Results: 150 patients<br />

presented between July 2008 and August 2011 were included in this<br />

analysis. Average age at diagnosis was 57 (range 30-87), and 56% <strong>of</strong><br />

patients were African <strong>American</strong>. Overall, 80% <strong>of</strong> the patients were vit D<br />

deficient at diagnosis, with levels � 30 ng/ml. African-<strong>American</strong> patients<br />

were more likely to be severely vit D deficient with levels � 10 ng/ml<br />

compared to Caucasians (33% vs. 7.5%, p� 0.0002). Patients with TNBC<br />

were more likely to be vit D deficient at diagnosis compared to hormone<br />

receptor-positive patients (93% vs. 76%, p �0.015). These patients also<br />

had the lowest mean (18) and median (16) <strong>of</strong> vit D levels compared to all<br />

other patients. This difference is also statistically significant in multivariate<br />

analysis when adjusted for age, race, and stage (OR 3.96; p�0.04).<br />

Regardless <strong>of</strong> the ER/PR status, Her 2 negative patients were more vit D<br />

deficient compared to Her 2 positive patients (86% vs. 61%, p�0.001).<br />

Unlike previous studies, no correlation was seen between tumor size and vit<br />

D levels. Furthermore, there is also no association between stage, nodal<br />

involvement, or Ki67 and vit D level. Conclusions: Vit D deficiency is<br />

common among patients with newly-diagnosed breast cancer, particularly<br />

African <strong>American</strong> patients. Patients with TNBC have a significantly higher<br />

likelihood <strong>of</strong> being vit D deficient than patients with other histological<br />

subtypes.<br />

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