Laura Biganzoli Oncologia Medica Nuovo Ospedale di Prato Istituto Toscano Tumori

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1 EFFECT: A randomized phase II study to evaluate the EFficacy and impact on Function of two different doses of nabpaclitaxel in elderly patients with advanced breast cancer Laura Biganzoli Oncologia Medica Nuovo Ospedale di Prato Istituto Toscano Tumori

2 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

3 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

4 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 A N=156 R B nab-paclitaxel 100mg/m 2 day1, 8, 15 q 28 nab-paclitaxel 125mg/m 2 day1, 8, 15 q 28 Stratification factors: Age vs 75 yrs Diabetes yes, no G3-4 CIRS-G yes, no IADL deficient yes, no till disease progression or toxicity

5 Primary endpoint: Study endpoints 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

6 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)

7 120 pts have been randomized as of Oct pts who received >1 cycle of nab-paclitaxel and have documented interruption of study treatment are eligible for analysis SIOG Conference. Prague 2015

8 Patient characteristics ADL, Activity of daily living; IADL, Instrumental ADL; CIRS-G, Cumulative Illness Rating Scale-Geriatrics

9 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

10 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

11 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 1 st pt randomized 30 Jan 2013

12 Back up

13 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 months

14 Statistical considerations