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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