nab-Paclitaxel

Sviluppi Futuri nel Carcinoma Mammario

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 II

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

GERMANY III

nab-Paclitaxel Studi Europei Ongoing

Trial Description Country Phase

Neoadjuvant chemotherapy with nab-paclitaxel in women with HER2-negative high-risk breast cancerETNA

ITALY III

A randomized phase II study evaluating three different schedules of nab-paclitaxel as first line chemoterapy in metastatic breast cancerSNAP

ITALY 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 cancerEFFECT

ITALY II

nab-Paclitaxel Studi “Ready to start”

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

bid, twice daily; IV, intravenous; MBC, metastatic breast cancer; q3w, every 3 weeks.

Nab-paclitaxel 150 mg/m2 IV in 30 min

GG 1-8 q3w

N = fino a 94Pazienti con ECOG PS 0-1, HER2-, inclusi TN, adeguata funzionalità d’organo6 cicli (+ 2 a discrezione del clinico)

N = fino a 94Pazienti con ECOG PS 0-1, HER2-, inclusi TN, adeguata funzionalità d’organo6 cicli (+ 2 a discrezione del clinico)

Studio GOIM Disegno dello Studio

+Capecitabina

825 mg/m2 Orale bidGG 1-14 q3w

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 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

Studio GEICAM Disegno dello studio

A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer

Studio GeparSepto

Primary endpoint: To compare pCR rates of neo-adjuvant treatment with nab-paclitaxel with solvent-based paclitaxelSecondary 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

12 weeks 12 weeksN = 1.200 R

Stratification:

- Subgroup HER2/HR - Ki67 - SPARC

Paclitaxel80 mg/m2 weekly

nab-Paclitaxel150 mg/m2 weekly

Epirubicin 90 mg/m2

Cyclophosphamide 600 mg/m2

If HER2-positive:

Trastuzumab 8 mg/kg (loading dose) followed by 6 mg/kg

Pertuzumab 840 mg (loading dose) followed by 420 mg

if HER2-positive:Trastuzumab

if HR-positive:Tamoxifen, Aromatase-Inhibitor

According to AGO recommendation

Core biopsy Core biopsyCore biopsy

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

Epirubicin 150mg/m2 q2w nab-Paclitaxel q2w Cyclophosphamide 2g /m2 q2w(Definition of dose by run-in Phase)

E

C C C C

E E E®

EC 90/600 mg/m², q2w x 4 Docetaxel 75 mg/m², q2w x 4 tailored tailored

D D D D

E E CE nP nPnP C C

R

+1week break

Pegfilgrastim q2w, Epoetin (Darbepoetin-α, Epoetin-β)

Pegfilgrastim q2w, Epoetin (Darbepoetin-α, Epoetin-β)

N=2.886

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

Studio ETNANeoadjuvant 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

ETNADisegno dello Studio

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 v4Feasibility: completing treatment according to the protocol for at least 24 weeksDisease control: stable disease for ≥24 weeks or confirmed overall partial response or complete responseOverall survival: time from randomization to death from any cause

Studio SNAP

SNAP Disegno dello Studio

• 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

nab-pac- 75 mg/m2 days 1,8,15,22

N=240

C

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 statusSecondary 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

nab-paclitaxel 125 mg/m2day 1, 8, 15 q 28

nab-paclitaxel 100mg/m2day 1, 8, 15 q 28

R

till disease progression or toxicityStratification factors: age 65-74 vs ≥ 75 yrs diabetes yes, no G3-4 CIRS 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 therapyNo prior CT for advanced breast cancerMeasurable or evaluable disease

N=156