408TiP - Pertuzumab and trastuzumab in combination with vinorelbine for first-line treatment of patients with HER2-positive locally advanced or metastatic br...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Presenter Michael Andersson
Authors M. Andersson1, J.M. Lopez-Vega2, L. Del Mastro3, T. Petit4, L. Mitchell5, C. Pelizon5, E.A. Perez6
  • 1Department Of Oncology, Rigshospitalet, 2100 - Copenhagen/DK
  • 2Servicio De Oncologia Medica, Hospital Universitario Marques de Valdecilla, Santander/ES
  • 3IRCCS AOU San Martino - IST-Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT
  • 4Centre De Lutte Contre Le Cancer, Centre Paul Strauss, FR-67065 - Strasbourg CEDEX/FR
  • 5., F. Hoffmann-La Roche Ltd, Basel/CH
  • 6Hematology / Oncology, Mayo Clinic, 32246 - Jacksonville/US

Abstract

Background

The humanised monoclonal antibody pertuzumab binds to the dimerisation domain of HER2, preventing heterodimerisation and downstream signalling. As pertuzumab is directed against a different epitope to trastuzumab, a more comprehensive HER2 blockade is achieved by combining the agents. The CLEOPATRA study showed significantly improved efficacy for pertuzumab and trastuzumab plus docetaxel, but pertuzumab with trastuzumab has not been tested with other chemotherapies in MBC. Trastuzumab plus vinorelbine (V) has comparable efficacy to trastuzumab plus docetaxel but with fewer adverse events. VELVET will assess the overall response rate (ORR) of pertuzumab with trastuzumab + V in first-line treatment of HER2-positive MBC. Administration of pertuzumab and trastuzumab in the same infusion bag will also be assessed.

Methods

VELVET is a multicentre, open-label, two-cohort, Phase II trial in patients (pts) with HER2-positive LABC/MBC not previously treated in the metastatic setting with non-hormonal anticancer therapy. Pts must have LVEF ≥55% and ECOG PS of 0/1. Enrolment began in April 2012 and 210 pts will be recruited. Cohort 1 (first 105 pts enrolled) will receive pertuzumab and trastuzumab sequentially, and Cohort 2 (next 105 pts) will receive pertuzumab and trastuzumab in the same infusion bag at Cycle 2 onwards assuming Cycle 1 was tolerated. V will be given in both cohorts. Treatment will continue until disease progression/unacceptable toxicity. Study doses (all iv): pertuzumab: 840 mg initial dose, 420 mg q3w; trastuzumab: 8 mg/kg initial dose, 6 mg/kg q3w, and V: 25 mg/m2 Day 1 and 8 (first cycle) then 30 − 35 mg/m2 Days 1 and 8 q3w (dose escalation at investigator discretion). Assuming best overall response of 70–80% and aiming at a distance from the estimated proportion to the CI limits of 8–11%, a total of 95 pts need to be evaluable per cohort (assuming withdrawal rate ∼10%). Primary endpoint is ORR by independent assessment. Secondary endpoints include investigator ORR assessment, time to response, duration of response, PFS, TTP, OS, safety/ tolerability and QoL.

Disclosure

T. Petit: I declare that have served on a advisory board for F. Hoffmann-La Roche.

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

C. Pelizon: I am currently an employee of F. Hoffmann-La Roche.

E.A. Perez: I declare that my institute has received research finding from Genentech, Sanofi Onc. and GSK.

All other authors have declared no conflicts of interest.