P1-17-01: Figitumumab Plus Exemestane Versus Exemestane as First-Line Treatment of Postmenopausal Hormone Receptor-Positive Advanced Breast Cancer: A Randomized, Open-Label Phase II Trial.

Abstract Background Figitumumab (CP-751,871) is a fully human IgG2 monoclonal antibody that inhibits IGF-1R. Exemestane profoundly reduces estrogen production and has activity as first-line treatment in postmenopausal metastatic hormone receptor-positive (HR+) breast cancer (BC). Preclinical studies suggest cross-talk between the IGF-1R and estrogen receptor pathways. Combining agents that inhibit these pathways could benefit women with advanced BC. Methods This was an open-label, multicenter, randomized, phase II trial of first-line figitumumab + exemestane (Arm A) vs. exemestane alone (Arm B) in HR+ postmenopausal advanced BC. Eligibility included: age >18 yrs with Stage IIIB or IV disease; baseline ECOG PS ≤2. A high rate of grade [G] 3 and 4 hyperglycemia after figitumumab treatment prompted a protocol amendment in February 2010 requiring patients (pts) to have a baseline HbA1c <5.7%. Patients received exemestane 25 mg po daily ± intravenous figitumumab 20 mg/kg every 21 days. The primary endpoint was progression-free survival (PFS) in pts with baseline HbA1c <5.7%. Secondary endpoints included clinical benefit rate (CBR) and safety. Results Between 2007 and February 2011, 103 pts were randomized to Arm A and 102 to Arm B. Of these, 37 pts in Arm A and 40 pts in Arm B had baseline HbA1c <5.7%. These data are from an unplanned interim analysis which preceded premature study termination by the Sponsor for clinical development reasons and to expedite availability of data collected to date. Baseline demographics were balanced between arms. PFS, CBR and safety are summarized in Table 1. The majority of AEs were G1/2. In the Arm A overall population, the most common G3/4 events (in decreasing frequency) were hyperglycemia, diabetes mellitus, weight loss, isolated GGT elevation and fatigue. Hyperglycemia was uncommon in Arm B and in all pts with HbA1c <5.7%.[Table 2]. Conclusions The addition of figitumumab to exemestane was tolerable but overall did not improve PFS compared with exemestane alone in pts eligible for this trial. However, a trend toward benefit with figitumumab combined with exemestane in pts without evidence of baseline metabolic syndrome (HbA1c <5.7%) was observed together with improved tolerability; further study with this combination may be warranted. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-17-01.