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

84s Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
TPS1142 General Poster Session (Board #36C), Sat, 8:00 AM-12:00 PM
NSABP B-47: A phase III trial of adjuvant therapy comparing chemotherapy
alone (six cycles of docetaxel plus cyclophosphamide or four cycles
of doxorubicin plus cyclophosphamide followed by weekly paclitaxel) to
chemotherapy plus trastuzumab in women with node-positive or high-risk,
node-negative, HER2-low invasive breast cancer. Presenting Author: Louis
Fehrenbacher, National Surgical Adjuvant Breast and Bowel Project and
Kaiser Permanente Northern California, Vallejo, CA
Background: Adjuvant studies utilizing trastuzumab in early HER2� breast
cancer demonstrated a large reduction in recurrence and death. Postenrollment
central testing showed HER2 non-amplified participants derived
similar benefit. Methods: Selection of one of the two chemotherapy
regimens is by physician choice: The non-anthracycline regimen is TC
(docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2) administered IV
every 3 weeks for 6 cycles; the anthracycline regimen is AC followed by WP
(doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered
IV either every 3 weeks or every 2 weeks [per investigator discretion] for 4
cycles followed by paclitaxel 80 mg/m2 IV weekly for 12 doses). Patients
are randomly assigned to receive chemotherapy with or without trastuzumab
therapy. For patients receiving the TC chemotherapy regimen,
trastuzumab is given every 3 weeks during and following chemotherapy
until 1 year after the first trastuzumab dose (8 mg/kg loading dose; 6 mg/kg
for the remaining doses). For patients receiving the AC followed by WP
chemotherapy regimen, trastuzumab begins with the first dose of weekly
paclitaxel and will be given weekly for 12 doses (4 mg/kg loading dose; 2
mg/kg for the remaining weekly doses). Following completion of WP,
trastuzumab therapy continues with 6 mg/kg doses given every 3 weeks for
a total of 1 year. Eligibility: Eligibility includes: node positive or high risk
node negative female breast cancer patients; HER2 IHC 1� or 2� scores,
but non amplified by FISH Statistical Design: The primary aim is to
determine whether the addition of trastuzumab to chemotherapy improves
invasive disease-free survival (IDFS). 3260 patients will be enrolled to
provide statistical power of 0.9 to detect a 33% reduction in the hazard rate
of IDFS using a one-sided alpha level of 0.025. Progress: Protocol was
activated in January 2011. As of January 27, 2012, 486 of 3260 patients
have been enrolled. Supported by NCI U10-12027, -37377, 69651,
69974, and Genentech, Inc.
TPS1144 General Poster Session (Board #36E), Sat, 8:00 AM-12:00 PM
ARTemis: Randomized trial with neoadjuvant chemotherapy for patients
with early breast cancer. Presenting Author: Helena Margaret Earl, Department
of Oncology, University of Cambridge, and NIHR Cambridge Biomedical
Research Centre, Cambridge, United Kingdom
Background: Bevacizumab is a new humanised monoclonal antibody which
targets vascular endothelial growth factor (VEGF) and thereby the neoangiogenic
process in cancer. Bevacizumab has shown promising anti-tumour
effect when given concurrently with taxane-based chemotherapy in breast
cancer. However two neoadjuvant breast cancer trials have produced
conflicting results. The NSABP-B40 study showed significant benefit for
bevacizumab only in the ER�ve patients (pathological complete response
(pCR) in ER�ve population 15.2% vs 23.3%, p�0.008). Whereas the
GEPARQUINTO trial reported significant benefit only in the triple negative
patients (pCR 27.8% vs 36.4% p�0.021). Methods: ARTemis is a phase
III randomised trial to determine whether the addition to neo-adjuvant
chemotherapy of bevacizumab is more effective than standard chemotherapy
alone in patients with HER2-negative early breast cancer. A total of
400 patients will be randomised into each of the two treatment arms which
will allow an absolute difference in the pCR rates in excess of 10% to be
detected at the 5% (2-sided) level of significance with an 85% power.
Primary outcome is pathological complete response rates after neoadjuvant
chemotherapy, i.e. no residual invasive carcinoma in the breast,
and no evidence of metastatic disease within the lymph nodes. Secondary
outcomes are disease free survival, overall survival, complete pathological
response rates in breast alone, radiological response after 3 and 6 cycles of
chemotherapy and rate of breast conservation and toxicities. Results:
Recruitment into ARTemis began in April 2009 and as of January 2012
had recruited 469 (59%). ARTemis is due to complete recruitment by Dec
2012 and the first planned interim analysis of the primary outcome will be
Dec 2013. Conclusion: The IDSMC reviewed the trial in June 2011 and
recommended continuation of recruitment to this important trial given
there were no safety concerns, and results from the other neoadjuvant
studies (NSABP-B40 and GEPARQUINTO) are conflicting.
TPS1143 General Poster Session (Board #36D), Sat, 8:00 AM-12:00 PM
IBL2001: Phase (ph) I/II study of a novel dose-dense (dd) schedule of
indibulin for the treatment of metastastic breast cancer. Presenting Author:
Tiffany A. Traina, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Indibulin (Zybulin, ZIO-301) is a new, synthetic agent that
inhibits tumor cell growth at the G2/M phase through destabilization of
microtubule dynamics. It binds tubulin at a different site than taxanes and
vinca alkaloids. Indibulin does not interact with acetylated (neuronal)
tubulins and has not exhibited the neurotoxicity associated with other
tubulin binders. Indibulin has potent antitumor activity in human cancer
cell lines, including multidrug-, taxane-, and vinblastine-resistant lines.
Norton-Simon modeling based on cell line data suggested that dd administration
could optimize efficacy while limiting toxicity. Methods: Eligible are
patients (pts) with metastatic or unresectable locally advanced breast
cancer, measurable or non-measurable disease, and any number of prior
therapies. The objective of the Ph I portion is to determine the maximum
tolerated dose (MTD) of indibulin when given in a dd fashion (5 days
treatment, 9 days rest (14 total) using standard 3�3 dose escalation
schema. Ph II will seek to estimate the proportion of pts progression free at
4 months when treated with indibulin at the dose determined in the Ph I.
Secondary endpoints are overall response rate, proportion of subjects with
stable disease �6 months and toxicity profile of indibulin. Optimal Simon
two-stage design with an unpromising rate of pts who have not progressed
at four months as 20% and a promising rate of 40% with a type I error of
5% and power of 80% will be used. 13 pts will initially enter the 1st stage of
the ph II portion. If there are 3 or fewer pts who do not experience disease
progression at 4 months in the first stage of ph II, the study will be
terminated and declared to have a negative result. If 4 or more pts do not
progress at 4 months, enrollment in the ph II of the study will be extended
to 43 pts. A total of 45 pts will be enrolled to allow for a 5% drop out rate to
account for pts who may not be evaluable for the primary endpoint due to
toxicity or study withdrawal rather than progression of disease or death prior
to 4 months. If �13 out of 43 pts are progression-free at 4 months, the
study will be considered to have a positive result and indibulin would be
considered worthy of further testing in this disease.
TPS1145 General Poster Session (Board #37A), Sat, 8:00 AM-12:00 PM
A phase II, single-arm, feasibility study of dose-dense doxorubicin and
cyclophosphamide (AC) followed by eribulin mesylate for the adjuvant
treatment of early-stage breast cancer (EBC). Presenting Author: Tiffany A.
Traina, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Randomized trials have confirmed the benefit of the combination
of an anthracycline (A) and cyclophosphamide (C) for the adjuvant
treatment of EBC. The addition of taxane therapy to AC therapy has further
improved survival. Despite the improvement in adjuvant therapies for BC,
new approaches for improving outcomes are of significant importance and
may involve developing improved combination regimens. Eribulin mesylate
has demonstrated antitumor activity and significant improvement in overall
survival (OS) in patients with heavily pretreated locally advanced or
metastatic breast cancer (MBC) and may improve outcomes in EBC as well.
Methods: This study will determine the feasibility of eribulin as adjuvant
therapy following dose-dense AC for HER2 normal EBC. A completion rate
of �80% was set as a threshold for feasibility as established adjuvant
regimens have shown feasibility rates ranging from ~65% for trastuzumab
to �80%. This is a phase 2, single-center, feasibility study of dose-dense
adjuvant chemotherapy in patients with EBC. Dose-dense AC (Doxorubicin
60 mg/m2 IV plus C 600 mg/m2 IV) on day 1 of every 14-day cycle is given
for 4 cycles, followed by 4 cycles of eribulin mesylate at 1.4 mg/m2 over
2-5 minutes IV on days 1 and 8 every 21 days. Growth factors are given on
day 2 of AC cycles and only for neutropenia events with eribulin treatment.
Feasibility is determined by the ability to complete the eribulin portion of
the regimen without a dose delay or reduction. Exploratory objectives
include efficacy endpoints of 3-year disease-free survival (DFS) and OS.
Patients have histologically confirmed HER2 normal stage I-III invasive
disease and adequate bone marrow, liver, and renal function. Thirty two of
approximately 80 planned patients are currently enrolled. Feasibility rates
will be calculated with growth factor support (ie, the successful use of
growth factor support following a neutropenia event is not considered a
dose delay)and without growth factor support (ie, where need for growth
factors is considered a delay). Secondary endpoints include DFS and OS
and will be estimated by Kaplan-Meier method.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.