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Abstract 5323
tnAcity: A Phase II/III Trial of Weekly nab-Paclitaxel Plus Gemcitabine or Carboplatin vs Gemcitabine-Carboplatin
as First-Line Treatment for Metastatic Triple-Negative Breast Cancer
Pierfranco Conte,1 Denise A. Yardley,2,3 Adam Brufsky,4 Robert E. Coleman,5 Javier Cortes,6 Stefan Glück,7 Jean-Marc A. Nabholtz,8 Joyce O’Shaughnessy,9 Li Li,10 JulieAnn Miller,10 Debora Barton,10 Nadia Harbeck,11 on behalf of the tnAcity Investigators
of Padova, Padova, Italy; 2Sarah Cannon Research Institute, Nashville, TN, USA; 3Tennessee Oncology, PLLC, Nashville, TN, USA; 4University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 5Weston Park Hospital, Sheffield Cancer Research Centre, Sheffield, England;
Hospital Vall d’Hebron, Barcelona, Spain; 7University of Miami, Miami, FL, USA; 8Centre de Lutte Contre le Cancer d’Auvergne, Clermont Ferrand, France; 9US Oncology, Dallas, TX, USA; 10Celgene Corporation, Summit, NJ, USA; 11Breast Center, University of Munich, Munich, Germany
1University
6University
INTRODUCTION
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ClinicalTrials.gov NCT01881230
First-line
triple-negative
metastatic breast
cancer
nab® is a registered trademark of Celgene Corporation.
nab-P 125 mg/m2
+ Gem 1000 mg/m2
d1, 8 q3w
(n = 80)
nab-P 125 mg/m2
+ Carbo AUC 2
d1, 8 q3w
(n = 80)
OBJECTIVES
Phase II
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Gem 1000 mg/m2
+ Carbo AUC 2
d1, 8 q3w
(n = 80)
To evaluate efficacy and risk profiles of the 2 nab-P experimental arms and
to identify the nab-P combination that will be used in the phase III portion of
the study
Phase III
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To compare the PFS of the selected nab-P regimen from the phase II portion
with that of Gem + Carbo
ENDPOINTS
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Primary: investigator-assessed PFSa
Secondary: investigator-assessed ORR,a percentage of patients initiating
cycle 6, OS, safety
Exploratory: time to second-line therapy or death; tumor analyses, including
protein, gene expression/mutations, receptor/biomarker assessment to
determine potential correlations with efficacy; and CTC levels in patients
who agree to participate
Phase III
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a
Primary: PFS by independent radiologist assessmenta
Secondary: ORR, OS, investigator-assessed PFS, DCR, DOR, safety
Exploratory: time to second-line therapy or death, healthcare resource
utilization, QOL, analysis of tumor samples in patients who agree to
participate (as in phase II)
By RECIST version 1.1.
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Gem 1000 mg/m2
+ Carbo AUC 2
d1, 8 q3w
(n = 275)
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Female, aged ≥ 18 years
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ECOG PS 0 - 1
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Must have received previous adjuvant or neoadjuvant anthracycline therapy unless
not indicated by physician or other appropriate regimens were administered
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Pathologically confirmed TNBC
Measurable metastatic disease
ER and PgR expression both < 1% of tumor cell nuclei per ASCO/CAP guidelinesa
a
HER2− per ASCO/CAP guidelinesa (IHC 0 or 1+ or FISH−, or IHC 2+ and FISH−)
Prior ER/PgR/HER2+ BC history; must have pathologically confirmed TN disease in
≥ 1 metastatic site
No prior cytotoxic chemotherapy for metastatic disease; prior radiation therapy
allowed
Patients in phase II are not part of the phase III population.
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Completion of prior neoadjuvant or adjuvant chemotherapy ≥ 6 months before
randomization or ≥ 12 months if containing taxane, Gem, or platinum agents
Monotherapy is allowed in the event of hypersensitivity or toxicity to one of
the treatment components
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Treatment modification or interruption should be limited to the component
associated with the specific toxicity; treatment with the other component
should continue per the protocol
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Concurrent chemotherapy or any other antitumor BC therapy
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History or current evidence of brain metastasis, including leptomeningeal
involvement
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History of other primary malignancy in the past 5 years, except prior history of
breast or in situ/basal/localized squamous cell skin cancer
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Baseline peripheral neuropathy grade ≥ 2 by NCI CTCAE v4.0
Prior immunotherapy or monoclonal antibody therapy for MBC is acceptable
Receipt of prior cytotoxic chemotherapy after incomplete resection of locoregional
recurrent disease
Regional lymph node as the only site of metastatic disease
Corresponding author’s email address: [email protected]
PC: Nothing to disclose; DAY: Nothing to disclose; AB: Consulting fees (Celgene); REC: Nothing to disclose; JC: Consulting fees
(Celgene, Novartis), fees for non-CME services (Roche, Celgene, Novartis, Eisai); SG: Consulting fees (Agendia, Genomic Health,
Celgene, Eisai, Genentech, Dara), contracted research (Agendia, Genomic Health, Celgene, Eisai, Genentech, Dara); J-MAN:
Nothing to disclose; JO: Consulting fees (Genentech, Sanofi US, Boehringer Ingelheim Int GmbH, BMS, Caris Diagnostics, Eisai,
GSK, J&J, Roche), fees for non-CME services (BMS, Celgene, Eisai, Genentech); LL: Employee and stock ownership (Celgene);
JM: Employee and stock ownership (Celgene); DB: Employee and stock ownership (Celgene); NH: Consulting fees (Celgene), fees
for CME services (Celgene).
TREATMENT MODIFICATIONS
Newly diagnosed TNMBC if anthracycline not indicated by physician
Key Exclusion Criteria
The tnAcity trial will investigate 2 nab-P–based combination regimens vs
Gem plus Carbo as first-line treatment for TNMBC
Phase II patients will be enrolled internationally in North America, Europe,
Latin America, and Australia
Biomarker analyses may advance the current understanding of TNBC
biology and response to treatment
This study may identify a nab-P–based cytotoxic chemotherapy combination
as a new first-line standard treatment regimen for TNMBC
Disclosures
Treatment until disease progression or unacceptable toxicity in both phases.
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Poster presented at the European Society for Medical Oncology 2014 Congress; September 26-30, 2014; Madrid, Spain
CONCLUSIONS
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Acknowledgments
METHODS
2013 preferred, 2007 acceptable.
Selected nab-P regimen from phase II
(n = 275)
A sample size of 80 patients per arm was selected for the phase II segment
to permit qualitative comparisons of toxicity between the 2 nab-P arms and
to provide preliminary data on antitumor activity
This should provide approximately 80% marginal power with a 2-sided
significance level of 0.2 to differentiate the regimens, assuming a median
PFS of 4.6 months for Gem + Carbo
The efficacy of the 3 arms of the phase 2 portion will be explored by
pairwise comparisons when a total of 96 PFS events have been observed
The phase III design to enroll 550 patients (330 PFS events) provides ≈ 90%
power to detect a hazard ratio of 0.70 for PFS with a 2-sided 5%
significance level, which represents a 43% improvement in median PFS for
the nab-P arm, assuming the median PFS is 4.6 months in the control arm
Current enrollment is 82 patients
This study is supported by Celgene Corporation, Summit, NJ. The authors received editorial and production support in the
preparation of this poster from MediTech Media, Ltd, funded by Celgene Corporation. The authors are fully responsible for all
content and editorial decisions for this poster.
Phase II: DFI: ≤ 1 year vs > 1 year
Phase III: DFI: ≤ 1 year vs > 1 year; prior adjuvant or neoadjuvant taxane treatment (Yes/No)
Key Inclusion Criteria
a
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Stratification factors:
Phase II
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Phase IIIa (n = 550)
Phase II (n = 240)
RANDOMIZE
1:1
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nab-P arm selected by
combination of efficacy + safety
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STATISTICAL ANALYSIS
STUDY DESIGN
Triple-negative breast cancer (TNBC) has a poor prognosis and an
aggressive clinical course compared with other subtypes of BC1-3
- Poorly differentiated tumors, early disease recurrence, and low survival
rates
TNBC is characterized by a lack of ER, PgR, and HER2 overexpression4
Although no standard of care has been identified, chemotherapy—including
taxane-based regimens—is recommended in the current NCCN treatment
guidelines for TNBC5
The FDA has approved 2 taxane-containing cytotoxic combination therapies
for the treatment of MBC, including capecitabine-docetaxel and gemcitabine
(Gem)-paclitaxel6-8
A median PFS of 4.6 months was reported in a phase III trial of patients with
TNMBC treated with first-line Gem + carboplatin (Carbo)9
Albumin-bound paclitaxel (nab®-paclitaxel [nab-P]) was approved for the
treatment of MBC or relapse within 6 months of adjuvant chemotherapy after
demonstrating favorable efficacy and safety vs solvent-based paclitaxel in a
phase III trial10,11
In phase II trials, nab-P, in combination with Gem or Carbo with or without
bevacizumab, has demonstrated efficacy and safety as first-line therapy for
MBC12-14
RANDOMIZE
1:1:1
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AUC, area under the curve; CAP, College of American Pathologists; CME, continuing medical education; CTC,
circulating tumor cell; DCR, disease control rate; DFI, disease-free interval; DOR, duration of response; ECOG PS,
Eastern Cooperative Oncology Group performance status; ER, estrogen receptor; FDA, US Food and Drug
Administration; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC,
immunohistochemistry; MBC, metastatic breast cancer; NCCN, National Comprehensive Cancer Network; NCI
CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; ORR, overall response rate; OS,
overall survival; PFS, progression-free survival; PgR, progesterone receptor; q3w, every 3 weeks; QOL, quality of life;
RECIST, Response Evaluation Criteria In Solid Tumors; TN, triple negative; TNMBC, triple-negative metastatic breast
cancer.
References
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