nab-Paclitaxel Sviluppi Futuri nel Carcinoma Mammario

nab-Paclitaxel Studi Europei Ongoing Trial Description Country Phase A multicenter phase II trial of nab-paclitaxel and Capecitabine as first line treatment in HER2 negative metastatic breast cancer ITALY II A phase II, open-label, non-randomized study of nab-paclitaxel for patients with stage II and III luminal breast cancer as neo-adjuvant treatment SPAIN A Randomized Phase III Trial Comparing Nanoparticle-based Paclitaxel With Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Patients With Early Breast Cancer (Gepar Septo) GERMANY III Adjuvant phase III trial to compare intense dose-dense treatment with EnPC to dose-dense, tailored therapy with dtEC-dtD for patients with high-risk primary breast cancer

nab-Paclitaxel Studi “Ready to start” Trial Description Country Phase Neoadjuvant chemotherapy with nab-paclitaxel in women with HER2-negative high-risk breast cancer ETNA ITALY III A randomized phase II study evaluating three different schedules of nab-paclitaxel as first line chemoterapy in metastatic breast cancer SNAP II 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 EFFECT

Studio GOIM A multicenter phase II trial of nab-paclitaxel and Capecitabine as first line treatment in HER2 negative Metastatic Breast Cancer Primary endpoint: The efficacy of combination in terms of response rate (RR) according to RECIST criteria The progression free survival (PFS) Secondary endpoints: Overall survival (OS) Tolerability and safety of the combination regimen according to CTC criteria

Studio GOIM Disegno dello Studio Nab-paclitaxel 150 mg/m2 IV in 30 min GG 1-8 q3w Capecitabina 825 mg/m2 Orale bid GG 1-14 q3w + N = fino a 94 Pazienti con ECOG PS 0-1, HER2-, inclusi TN, adeguata funzionalità d’organo 6 cicli (+ 2 a discrezione del clinico) bid, twice daily; IV, intravenous; MBC, metastatic breast cancer; q3w, every 3 weeks.

Studio GEICAM A phase II, open-label, non-randomized study of nab-paclitaxel for patients with stage II and III luminal breast cancer as neo-adjuvant treatment Study GEICAM is a multicenter, open label, non-randomized phase 2 trial to evaluate the efficacy and safety of nab-Paclitaxel in the neoadjuvant treatment of ER positive HER2 negative patients amenable to receive neoadjuvant chemotherapy Primary endpoint: Determine percentage of patients with poor response in contrast to good response (residual cancer burden) Secondary endpoints: pCRR after surgery, Clinical response (RECIST), Invasive disease-free survival, Correlation of Ki67, gp-60, caveolin-1, SPARC and PAM50 gene expression assay with efficacy, Tolerability

Studio GEICAM Disegno dello studio 52 5 MA 1219 00004762 2007 04 26 - 03:46:51 PM ESA 1256 2007 10 01 - 12:05:26 PM 69 5 7

Studio GeparSepto A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer Primary endpoint: To compare pCR rates of neo-adjuvant treatment with nab-paclitaxel with solvent-based paclitaxel Secondary endpoints: Assess the pCR rates for stratified subgroups, Assess various pCR rates, Determine response rates of breast tumor and axillary nodes, Clinical remission rate by taxane use, Rate of breast conservative surgery, Toxicity and compliance, Determine pCR and LRFS in patients with a cCR and a negative core biopsy before surgery

GeparSepto Disegno dello Studio Core biopsy Core biopsy Core biopsy Surgery if HER2-positive: Trastuzumab if HR-positive: Tamoxifen, Aromatase-Inhibitor According to AGO recommendation N = 1.200 R 12 weeks 12 weeks Stratification: - Subgroup HER2/HR - Ki67 - SPARC If HER2-positive: Trastuzumab 8 mg/kg (loading dose) followed by 6 mg/kg Pertuzumab 840 mg (loading dose) followed by 420 mg Paclitaxel 80 mg/m2 weekly nab-Paclitaxel 150 mg/m2 weekly Epirubicin 90 mg/m2 Cyclophosphamide 600 mg/m2

Studio GeparSepto Disegno dello studio

Studio GAIN II Adjuvant phase III trial to compare intense dose-dense treatment with EnPC to dose-dense, tailored therapy with dtEC-dtD for patients with high-risk primary breast cancer Primary endpoint: Invasive disease free survival (IDFS) Secondary endpoints: DDFS and OS, Brain metastasis free survival (in the subgroups of TNBC and HER2+ breast cancer patients), Compliance and safety, Quality of life

GAIN II Disegno dello Studio nP nP nP C C C Pegfilgrastim q2w, Epoetin (Darbepoetin-α, Epoetin-β) N=2.886 ® Epirubicin 150mg/m2 q2w nab-Paclitaxel q2w Cyclophosphamide 2g /m2 q2w (Definition of dose by run-in Phase) R E E E E +1 week break D D D D C C C C Pegfilgrastim q2w, Epoetin (Darbepoetin-α, Epoetin-β) EC 90/600 mg/m², q2w x 4 Docetaxel 75 mg/m², q2w x 4 tailored tailored

Studio ETNA Neoadjuvant chemotherapy with nab-paclitaxel in women with HER2-negative high-risk breast cancer Adapted from STRATEGIES for SELECTING THERAPY in HERNEGATIVE BREAST CANCER, ESMO Vienna 2012, prIME Oncology activity Satellite Symposium

Studio ETNA Adapted from STRATEGIES for SELECTING THERAPY in HERNEGATIVE BREAST CANCER, ESMO Vienna 2012, prIME Oncology activity Satellite Symposium

ETNA Disegno dello Studio Adapted from STRATEGIES for SELECTING THERAPY in HERNEGATIVE BREAST CANCER, ESMO Vienna 2012, prIME Oncology activity Satellite Symposium

Studio SNAP A randomized phase II study evaluating three different schedules of nab-paclitaxel in metastatic breast cancer Primary endpoint: Progression Free Survival (PFS) Secondary endpoints: Adverse events according to CTCAE v4 Feasibility: completing treatment according to the protocol for at least 24 weeks Disease control: stable disease for ≥24 weeks or confirmed overall partial response or complete response Overall survival: time from randomization to death from any cause

SNAP Disegno dello Studio nab-pac- 75 mg/m2 days 1,8,15,22 C Randomization allocation 1:1:1 (A:B:C) Note that the schedules of 150 mg/m2 differ in induction (days 1,8,15) and maintenance arm B (days 1,15) nab-paclitaxel administered in 28 day cycles Continue treatment until progressive disease (PD) or unacceptable toxicity

Studio 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 Primary endpoint: Event-free survival (EFS) where an event is either disease progression or death or decline in functional status 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)

EFFECT Disegno dello Studio 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 yes, no IADL deficient yes, no