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

TPS1146 General Poster Session (Board #37B), Sat, 8:00 AM-12:00 PM
DETECT III: A multicenter, randomized, phase III study to compare
standard therapy alone versus standard therapy plus lapatinib in patients
(pts) with initially HER2-negative metastatic breast cancer but with
HER2-positive circulating tumor cells (CTC). Presenting Author: Carsten
Hagenbeck, Department of Gynecology and Obstetrics, Heinrich Heine
University, Duesseldorf, Germany
Background: HER2 status may change over the course of disease in breast
cancer pts. Approx. 20-30% of pts with initially HER2-negative breast
cancer have HER2-positive metastasis (Zidan et al. 2005; Tewes et al.
2009). Determining HER2 status on CTC is one option to re-evaluate HER2
status at the time metastasis is diagnosed. Currently it is unclear if
HER2-targeted therapy based on the assessment of HER2 status of CTC
reveals a clinical benefit. Methods: This is a randomized, open-label, two
arm phase III study to investigate the clinical efficacy of lapatinib, as a
HER2-targeted therapy in initially HER2-negative metastatic breast cancer
pts with HER2-positive CTC at the time of distant disease. As only half of
the pts with HER2-negative metastatic breast cancer show CTC-positivity
and of those approx. 32% will exhibit HER2-positive CTC (Fehm et al.
2010), screening of about 1420 pts is required to enroll 228 pts. Main
inclusion criteria: metastatic breast cancer with HER2-negative primary
tumor tissue and/or biopsies from metastatic sites or locoregional recurrences,
evidence of �1 HER2-positive CTC and �1 measurable metastatic
lesion according to RECIST. Eligible pts will be randomized 1:1 to receive
standard treatment vs. standard treatment plus lapatinib. Standard chemoor
endocrine therapy must be approved in combination with lapatinib or
been investigated in prior clinical trials. Primary endpoint is progression
free survival. Secondary endpoints include overall response rate, clinical
benefit rate, overall survival and dynamic of CTC. The DETECT III trial is
one of the first trials where treatment is based on phenotypic characteristics
of CTC. If this trial succeeds in proving efficacy of lapatinib in pts with
initially HER2-negative metastatic breast cancer but HER2-positive CTC,
this will establish a new strategy in the treatment of metastatic breast
cancer.
TPS1148 General Poster Session (Board #37D), Sat, 8:00 AM-12:00 PM
Phase II study of the multikinase inhibitor dovitinib (TKI258) or placebo in
combination with fulvestrant in postmenopausal, endocrine resistant
HER2-/HR� breast cancer. Presenting Author: Fabrice Andre, Institut
Gustave Roussy, Villejuif, France
Background: Overcoming endocrine resistance is a critical goal in the
treatment of hormone receptor�positive (HR�) breast cancer. Molecular
mechanisms associated with endocrine resistance include adaptive “crosstalk”
between the estrogen receptor and the fibroblast growth factor
receptor (FGFR). Up to 8% of HR�/HER2- breast cancer patients (pts)
have amplification of the FGFR1 gene, which is associated with resistance
to endocrine therapy but can be overcome via FGFR1 inhibition in
preclinical models. Dovitinib is a potent FGF, VEGF, and PDGF receptor
tyrosine kinase inhibitor that demonstrated antitumor activity in heavily
pretreated breast cancer pts with FGF pathway amplification (FGFR1,
FGFR2, or ligand FGF3; Andre et al, ASCO 2011). Dovitinib may reverse
resistance to endocrine therapy related to FGF-pathway amplification and
is studied here to determine if it can improve outcomes when combined
with fulvestrant. Methods: Postmenopausal HER2-/HR� locally advanced
or metastatic breast cancer pts (N»150) progressing within 12 months of
completion of adjuvant endocrine therapy or after � 1 prior endocrine
therapy in the advanced setting will be enrolled in this multicenter,
randomized, double blind, placebo controlled, phase II trial. Pts will
prospectively undergo molecular screening to enrich for FGF-amplification
(FGFR1, FGFR2, orFGF3 amplification by qPCR; 45 amplified and 30
non-amplified pts per arm). Pts will be randomized 1:1 to receive
fulvestrant (500 mg q4w [with an additional dose 2 wks after the initial
dose]) in combination with oral dovitinib (500 mg, 5 days on/2 days off) or
placebo until disease progression, unacceptable toxicity, or death. The
primary endpoint is progression-free survival, with tumor assessments
performed q8w. Secondary endpoints include overall response rate per
RECIST v1.1, duration of response, overall survival, ECOG performance
status and patient reported outcome scores over time, and safety. The
pharmacodynamic effect of dovitinib on FGFR-associated angiogenic
pathways in tumor specimens and potential predictive biomarkers of
response to dovitinib will be explored.
Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
85s
TPS1147 General Poster Session (Board #37C), Sat, 8:00 AM-12:00 PM
A multicenter prospective study of image-guided radiofrequency ablation
for small breast carcinomas. Presenting Author: Takayuki Kinoshita,
National Cancer Center Hospital, Tokyo, Japan
Background: As the management of breast carcinoma evolves toward less
invasive treatments, the next step is the possibility of removing the primary
tumor without surgery. The most promising noninvasive ablation technique
is radiofrequency ablation (RFA), which can effectively kill tumor cells with
a low complication rate. Our preliminary studies of RFA followed by
standard surgical resection have indicated that this technique is effective
for surgical ablation of small (� 2cm) breast tumors without extensive
intraductal components (EIC). Methods: To determine if RFA is oncologically
and cosmetically appropriate for the local treatment of primary breast
carcinoma, this multi-center prospective study used RFA as the sole local
treatment of breast tumors � 1.5cm in size on ultrasound and MRI.
Exclusion criteria include receiving of preoperative chemotherapy, or the
presence of invasive lobular carcinoma or invasive ductal carcinoma with
suspicious EIC. After confirmation that the standard baseline core biopsy
for diagnosis and measurement of tumors markers (ER, PgR, HER-2/neu
expression and the presence of the Ki-67 proliferative marker) have been
obtained, consent will be obtained and the patient scheduled RFA. All
patients received adjuvant radiation therapy. The use and choice of
systemic therapy will be based on the information from the baseline core
biopsy and imaging studies. The first primary endpoints of this study is
successful tumor ablation, as evidenced by negative findings on vacuumassisted
or core biopsies and imaging studies after RFA. The second
primary endpoints is the incidence of procedure related adverse events.
Forty patients with small tumors that are clearly identifiable and measurable
by ultrasound and MRI were enrolled. The response to ablation was
evaluated with both vacuum-assisted or core biopsies and imaging studies
every 3 months during the first year. The long-term outcomes were assessed
using quality of life measurement scales and imaging studies every 6
months thereafter through year 5.
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