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

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. 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

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

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 65-74 vs ≥ 75 yrs Diabetes yes, no   G3-4 CIRS-G yes, no IADL deficient yes, no

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)

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

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Statistical considerations