409TiP - Pertuzumab in combination with trastuzumab and a taxane for the first-line treatment of patients with HER2-positive advanced breast cancer: a single...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter David Miles
Authors D. Miles1, T. Peretz-Yablonski2, E. Ciruelos3, F. Puglisi4, A. Schneeweiss5, L. Mitchell6, A. Dünne6, T. Bachelot7
  • 1Medical Oncology, Mount Vernon Cancer Center, HA6 2 RN - Northwood/UK
  • 2Hadassah University Hospital, IL-91120 - Jerusalem/IL
  • 3Medical Oncology, Hopital 12 de Octubre, Madrid/ES
  • 4Dipartimento Di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine/IT
  • 5Gynecological Oncology, National Center for Tumor Diseases, Heidelberg/DE
  • 6., F. Hoffmann-La Roche Ltd, Basel/CH
  • 7INSERM, Lyon/FR

Abstract

Background

Pertuzumab (P) inhibits downstream signaling of HER2 by preventing its heterodimerization with other HER family members. The epitope recognized by P is distinct from that bound by trastuzumab (H) and their complementary mechanisms of action lead to a more comprehensive HER2 blockade when combined. Data from the phase III trial CLEOPATRA showed significantly improved PFS in pts with HER2-positive 1L MBC given P + H + docetaxel (D). As H was not widely available in the (neo)adjuvant setting prior to CLEOPATRA recruitment, a relatively low proportion of pts in CLEOPATRA had previously received H. PERUSE will assess the safety and tolerability of P + H + one of a choice of taxanes (T) as 1L therapy for pts with HER2-positive metastatic or locally advanced BC. Efficacy endpoints will also be recorded in PERUSE, in a pt population likely to have experienced wider exposure to prior H therapy.

Methods

PERUSE is a phase IIIb, multicenter, open-label, single-arm study in pts with HER2-positive BC who have not been treated with systemic non-hormonal anticancer therapy for MBC. The planned sample size is 1500. Pts will receive, P: 840mg initial dose, 420mg q3w IV; H: 8mg/kg initial dose, 6mg/kg q3w IV, T: D, paclitaxel or nab-paclitaxel according to local guidelines. A planned protocol amendment will allow HR-positive pts to receive endocrine therapy in conjunction with P + H following completion of T in line with clinical practice. Treatment will be administered until disease progression or unacceptable toxicity. At baseline, pts must have an LVEF of ≥50%, ECOG PS of 0, 1 or 2 and must not have received prior anti-HER2 agents for MBC. Prior H and/or lapatinib in the (neo)adjuvant setting is allowed, provided there was no disease progression on-treatment. A disease-free interval of ≥6 months is required. The primary endpoint is safety and tolerability. Secondary endpoints include PFS, OS, ORR, CBR, duration of response, time to response and QoL. The final analysis will be carried out when pts have been followed up for ≥12 months. Interim analyses are planned after enrollment of ∼350, 700 and 1000 pts. Regular interim safety assessments by a DSMB will take place.

Disclosure

D. Miles: I have an interest in relation with one organisation that could be perceived as a possible conflict of interest in the context of the subject of this abstract. I have served on Advisory Board Meetings for Roche/Genentech.

F. Puglisi: I have an interest in relation with one organisation that could be perceived as a possible conflict of interest in the context of the subject of this abstract. I participate in Advisory Board Meetings for Roche.

A. Schneeweiss: I have an interest in relation with one organisation that could be perceived as a possible conflict of interest in the context of the subject of this abstract. I serve on Roche Advisory Boards and am in volved with corporate-sponsored research with Roche.

L. Mitchell: I am currently an employee of F. Hoffmann-La Roche.

A. Dünne: I have an interest in relation with one organisation that could be perceived as a possible conflict of interest in the context of the subject of this abstract. I am an employee of hoffmann-La Roche.

T. Bachelot: I have an interest in relation with one organisation that could be perceived as a possible conflict of interest in the context of the subject of this abstract. I am involved with Roche sponsoredresearch and Roche advisory Board Meetings.

All other authors have declared no conflicts of interest.