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EFFECT: A randomized phase II study to evaluate the
EFficacy and impact on Function of two different doses of nab-
paclitaxEl in elderly patients with advanCed breasT cancer
Laura Biganzoli
Oncologia Medica
Nuovo Ospedale di Prato
Istituto Toscano Tumori
Background and rationale
• Elderly patients are at higher risk of chemotherapy
related side effects
• Weekly taxanes are generally recommended treatment
options in older metastatic breast cancer
• Fatigue and neurotoxicity are dose-limiting toxicity for
docetaxel and standard paclitaxel with a possible
negative impact on function
• Nab-paclitaxel compares favorably with paclitaxel and
docetaxel both in terms of safety and efficacy
• Median time to resolution to G<3 neurotoxicity is shorter
with nab-paclitaxel than with conventional taxanes
Background and rationale (I)
• Limited amount of data available on activity and safety of
nab-paclitaxel in older patients
Aapro et al. The Breast 2011
EFFECT: A randomized phase II study to evaluate the EFficacy
and impact on Function of two different doses of nab-paclitaxEl
in elderly patients with advanCed breasT cancer
nab-paclitaxel 100mg/m2
day 1, 8, 15 q 28
nab-paclitaxel 125mg/m2
day 1, 8, 15 q 28
R
till disease progression or toxicityStratification factors:
Age 65-74 vs ≥ 75 yrs
Diabetes yes, no
G3-4 CIRS-G yes, no
IADL deficient yes, no
Age ≥ 65
Locally recurrent or metastatic HER2-neg breast cancer or HER2-
positive but considered not eligible for anti-HER2 therapy
No prior CT for advanced breast cancer
Measurable or evaluable disease
N=156
A B
Study endpoints
• Primary endpoint:
Event-free survival (EFS) where an event is either
disease progression or death or decline in functional
status
Functional status will be measured using ADL and IADL at
baseline, prior to each treatment cycle, at treatment discontinuation
and at 4 weeks after the last cycle of chemotherapy
An ‘event’ is defined as a decrease in at least 1 point
with respect to values observed at the baseline on the ADL
and/or IADL scales, considered by the investigator to be
treatment related, and confirmed at the subsequent cycle
ADL, Activity of daily living; IADL, Instrumental ADL
Secondary endpoints
– Objective response rate (ORR)
– Clinical benefit rate (CBR)
– Progression free survival (PFS)
– Overall survival (OS)
– Incidence of Adverse events (defined by CTCAE
v4.0)
• 120 pts have been randomized as of Oct 2015
• 74 pts who received >1 cycle of nab-paclitaxel
and have documented interruption of study
treatment are eligible for analysis
SIOG Conference. Prague 2015
Patient characteristics
ADL, Activity of daily living; IADL, Instrumental ADL; CIRS-G, Cumulative Illness Rating Scale-Geriatrics
Treatment administration and
compliance
• Overall, 419 cycles have been delivered, 181 in Arm A
and 238 in Arm B
• Tx interruptions occurred in 20 pts due to tox, 4 (13%) in
Arm A and 16 (37%) in Arm B
Most common AE(incidence of ≥ 10% for G2 or any G3-4 in either arm)
• No G3/4 febrile neutropenic events
• No tx related deaths
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Accrual by participating center
CENTER N . patients
Opedale A.Perrino Brindisi 23*
AO Ospedali Riuniti Ancona 18*
AO S.Maria della Misericordia Udine 14
Spedali Civili Brescia 14
CRO di Aviano 11
AUSL 4 di Prato 10
AO Papa Giovanni XXIII Bergamo 10
ASL Frosinone 8
Fondazione S.Maugeri Pavia 4*
Ospedale Vito Fazzi Lecce 4
IOV Padova 4
Universita’di Napoli Federico II 2
IEO 2
AUSL 12 Viareggio 2
AOU Integrata Verona 1
TOTAL 127*
Expected 156
*3 pts never started per protocol therapy 1st pt randomized 30 Jan 2013
Back up
STATISTICAL CONSIDERATIONS
This study is designed to assess efficacy and impact on functional status as measured by
EFS in each treatment arm. This study is not designed to provide adequate power for a two arm comparison. The evaluation of the best appropriate dose will be based on clinical/general conditions.
In each treatment arm, the null hypothesis to be tested is that the median of the EFS time is equal to or less than 7 months. The alternative hypothesis is that the median of the EFS time is greater than 7 months. The study power will be at least 90% if the median of the EFS time is equal or greater than 12 months. The Kaplan-Meier approach will be used to estimate median EFS for each treatment arm. The hypothesis test will be conducted according to Brookmeyer and Crowley
NUMBER OF PATIENTS
The protocol will aim to accrue up to 156 patients with 78 patients randomized to Arm A, and 78 patients to Arm B.The expected enrollment period is approximately 24-30 months
Statistical considerations