Istituto Nazionale per la Ricerca sul Cancro Genoa – Italy Clinical trials in breast cancer in Italy: the Gruppo Italiano Mammella (GIM) Lucia Del Mastro Istituto Nazionale per la Ricerca sul Cancro Genoa – Italy Roma, 16 Novembre 2006

GIM group Intergroup: GONO-GOCSI-GOIRC-GOL Participating centers: 100 italian centers Main focus: phase III study in early breast cancer Chemotherapy Endocrine therapy Supportive care

Adjuvant chemotherapy trials Role of taxanes in node negative patients GIM-1 study Role of dose-dense and role of three-drug regimen as compared to two-drug regimen in taxane-containing chemotherapy in node positive patients GIM-2 study

GIM 1 study A phase III randomized study of sequential Epidoxorubicin plus Cyclophospamide followed by Docetaxel (ECD) versus the combination of 5-Fluorouracil, Epidoxorubicin and Cyclophospamide (FEC) as adjuvant treatment of node-negative early breast cancer patients

GIM 1: phase III randomized study EC 90/600 q21 x 4 DOCETAXEL 100 q21 x 4 FEC 600/75/600 q21 x 6

STUDY OBJECTIVES Primary objective: Secondary objective: to compare Disease Free Survival (DFS) between treatment groups Secondary objective: to compare Overall Survival (OS) to compare Safety

Study details Start date: 13/11/2003 Protocol status: ongoing Participating centers: 84 Total randomized patients: 842

Protocol GIM 2 A phase III randomized study of EC followed by Paclitaxel versus FEC followed by Paclitaxel, all given either every 3 weeks or 2 weeks supported by Pegfilgrastim, for node positive breast cancer patients

GIM-2: study design and objectives ARM A EC x 4  T x 4 q. 3 w ARM C EC x 4  T x 4 q. 2 w + Pegfilgrastim ARM B FEC x 4  T x 4 q. 3 w ARM D FEC x 4  T x 4 q. 2 w + Pegfilgrastim Factorial study aimed at assessing two separate hypothesis: Factor 1: A+C vs B+D = the efficacy and safety of 5-FU in addition to ECT Factor 2: A+B vs C+D = the efficacy and safety of a 50% increase in dose-density

Study objectives Primary objective: Secondary objective: to compare Disease Free Survival (DFS) from adding of 5-Fluorouracil to EC followed by Paclitaxel to compare Disease Free Survival (DFS) of schedule every 2 weeks versus 3 weeks Secondary objective: to compare Safety

Study details Start date: 20/03/2003 Protocol status: closed 03/07/2006 Participating centers: 91 Total randomized patients: 2091

A PHASE III STUDY IN POSTMENOPAUSAL WOMEN WITH EARLY BREAST CANCER PROTOCOL GIM4 LETROZOLE ADJUVANT THERAPY DURATION STUDY (LEAD): STANDARD VERSUS LONG TREATMENT with AROMATASE INHIBITORS A PHASE III STUDY IN POSTMENOPAUSAL WOMEN WITH EARLY BREAST CANCER

Phase III randomized study Study design Phase III randomized study Postmenopausal TAM 2-3 yrs LETROZOLE 5 YRS LETROZOLE 3-2 YRS

Study objectives Primary objective: Secondary objectives: to compare Disease Free Survival (DFS) between treatment groups Secondary objectives: to compare Overall Survival (OS) to compare Safety

Study details Start date: 27/07/05 Protocol status: ongoing Participating centers: 64 Total randomized patients: 500

PROTOCOL GIM-5 CYPLEC STUDY: CYP19 LETROZOLE CORRELATION STUDY Letrozole Extended-Adjuvant Therapy After Tamoxifen Study of Gene CYP19 Correlation with Letrozole Efficacy in Postmenopausal Early Breast Cancer Patients

CYPLEC – GIM 5 Multicenter, not comparative, prospective, phase IIIb study of GIM group Postmenopausal pts ER and/or PgR + Tamoxifen 4,5-6 yrs. Letrozole 5 years Registration Total Patients: 2400 during a 3-year period Primary objective: correlation between a Single Nucleotide Polymorphism (SNP) of CYP19 and Disease Free Survival (DFS) Hypothesis: 86% of power to detect a relative reduction of relapse of 46%: 4-yrs DFS for TC genotype = 91% 4-yrs DFS for CC or TT genotype = 95%

Study objectives PRIMARY OBJECTIVE SECONDARY OBJECTIVES Correlation DFS - SNP of CYP19 gene SECONDARY OBJECTIVES Correlation SNP of CYP19 gene and: 1) letrozole plasma concentration 2) aromatase inhibition by plasma estrone-S 3) OS 4) Safety

Study details Start date: 27/07/05 Protocol status: ongoing Participating centers: 64 Total enrolled patients: 162

A randomized phase III multicenter study Protocol Promise Prevention of chemotherapy – induced menopause by temporary ovarian suppression with Triptorelin vs control in young breast cancer patients. A randomized phase III multicenter study

Randomized phase III study Study design Randomized phase III study Age <45 yrs Stage I-II-III Candidate for chemotherapy Only CT CT + Triptorelin

Study Objectives Primary objective: Secondary objective: to evaluate efficacy of Triptorelin to prevent chemotherapy-induced amennorreha Secondary objective: to compare safety of chemotherapy associated to Triptorelin vs only chemotherapy

Study details Start date: 29/05/2003 Protocol status: ongoing Participating Centers: 24 Total randomized patients: 188