1. Lo sviluppo clinico di nab-paclitaxel Discussant: Fabio Puglisi
II Sessione - Gestione terapeutica del carcinoma della mammella: presente e futuro
Chair: S. De Placido - Moderatore: A. Di Leo
Lo sviluppo clinico di nab-paclitaxel Discussant: Fabio Puglisi
Studio EFFECT
Laura Biganzoli
Nuovo Ospedale di Prato

2. 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

3. Background and rationale
Elderly patients are at higher risk of chemotherapy related side effects. Aging is associated with reduced normal tissue tolerance to chemotherapy, such that older patients are at higher risk of both hematological and non-hematological toxicity.
Therefore the therapeutic index, the ratio of efficacy to toxicity, of a treatment may be different in older compared with younger patients

4. Background and rationale (I)
Nab-paclitaxel compares favorably with paclitaxel and docetaxel both in terms of safety and efficacy. Premedication with steroids is not required and median time to resolution to G<3 neurotoxicity is shorter with nab-paclitaxel than with conventional taxanes
These features make nab-paclitaxel a particularly interesting agent for evaluation in elderly patients
Limited amount of data available on activity and safety of nab-paclitaxel in older patients
Aapro et al. The Breast 2011

5. 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
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
nab-paclitaxel 125 mg/m2
day 1, 8, 15 q 28
nab-paclitaxel 100mg/m2 R
till disease progression or toxicity
Stratification factors:
Age vs ≥ 75 yrs
Diabetes yes, no  
G3-4 CIRS-G yes, no
IADL deficient yes, no

6. 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

7. 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)

8. Accrual by participating center
N . patients
Opedale A.Perrino Brindisi
19*
AO Ospedali Riuniti Ancona 14
AO  S.Maria della Misericordia Udine
CRO di Aviano 10
AUSL 4 di Prato 9
Spedali Civili Brescia 7
AO Papa Giovanni XXIII Bergamo
Ospedale Vito Fazzi Lecce 3
ASL Frosinone
Universita’di Napoli Federico II 2
Fondazione S.Maugeri Pavia 2*
AOU Integrata Verona 1
IOV Padova
TOTAL 92
*1 pt never started per protocol therapy

9. Back up

10. Statistical considerations