Abstract OT1-1-02: A single-arm phase IIIb study of pertuzumab and trastuzumab with a taxane as first-line therapy for patients with HER2-positive advanced breast cancer (PERUSE)
Authors: Bachelot T , Ciruelos E , Peretz-Yablonski T , Schneeweiss A , Puglisi F , Mitchell L , Dünne A , Miles D 
Published: August 2014

Abstract
Background: Pertuzumab (P), a humanized monoclonal antibody, inhibits signaling downstream of HER2 by binding to the dimerization domain of the receptor and preventing heterodimerization with other HER family members. The epitope recognized by P is distinct from that bound by trastuzumab (H) and so their complementary mechanisms of action result in a more comprehensive HER2 blockade. Data from the phase III trial CLEOPATRA showed significantly improved PFS in patients (pts) receiving P + H + docetaxel compared with H + docetaxel + placebo as first-line treatment for HER2-positive metastatic breast cancer (BC).
Trial design: PERUSE is a phase IIIb, multicenter, open-label, single-arm study in pts with HER2-positive metastatic or locally recurrent BC who have not been treated with systemic nonhormonal anticancer therapy for metastatic cancer. Pts will receive, P: 840 mg initial dose, 420 mg q3w IV; H: 8 mg/kg initial dose, 6 mg/kg q3w IV; taxane: docetaxel, paclitaxel, or nab-paclitaxel according to local guidelines. Treatment will be administered until disease progression or unacceptable toxicity. A planned protocol amendment will allow hormone receptor-positive pts to receive endocrine therapy alongside P+H after completion of taxane therapy, in line with clinical practice.
Eligibility criteria: At baseline, pts must have an LVEF of ≥50%, an ECOG PS of 0, 1, or 2, a disease-free interval of ≥6 months, and must not have received prior anti-HER2 agents for the treatment of metastatic BC. Prior H and/or lapatinib in the (neo)adjuvant setting is permitted, providing there was no disease progression during treatment. Pts must not have experienced other malignancies within the last 5 yrs other than carcinoma in situ of the cervix or basal cell carcinoma. There must be no clinical or radiographic evidence of CNS metastases or clinically significant cardiovascular disease.
Specific aims: 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 + choice of taxane as first-line therapy for pts with HER2-positive metastatic or locally advanced BC in a pt population likely to have experienced wider exposure to prior H therapy.
Statistical methods: The primary endpoints of the PERUSE study are safety and tolerability. Secondary endpoints include PFS, OS, ORR, CBR, duration of response, time to response and QoL. The final analysis will be performed when 1500 pts have been followed up for at least 12 months after the last pt receives last study treatment unless they have been lost to follow-up, withdrawn consent, or died, or if the study is prematurely terminated by the sponsor. Safety analyses are planned after enrollment of ∼350, 700, and 1000 pts. Additionally, a data and safety monitoring board will review safety data after ∼50 pts have been enrolled and then every 6 months.
Current and target accrual: Enrollment of the first pt is expected in June 2012 with a total of 1500 pts planned to be recruited.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-02.