TBCRC 001: EGFR inhibition with cetuximab added to carboplatin in metastatic triple-negative (basal-like) breast cancer

Abstract

1009 Background: Basal-like breast cancer (BBC) has low expression of ER, PR, and HER2, and is thus often called triple negative (TN). Preclinical studies suggest that BBC depend on EGFR/HER1 for proliferation. TBCRC 001 is a multicenter randomized phase II study of cetuximab (C) alone and combined with carboplatin (P) in TN metastatic BrCa (MBC). Methods: Eligibility required measurable disease, ≤ 3 prior chemotherapy, no prior platinum or EGFR inhibitor. Patients (pts) in Arm 1 received C alone (400 mg/m2, then 250 mg/m2 weekly) with P (AUC 2, 3 of 4 weeks) added upon progression (PD). Pts in Arm 2 received C+P throughout. Primary endpoint was objective response (RR, CR+PR). Results: 102 TN patients were enrolled; Arm 1 = 31 pts (closed in 3/07), Arm 2 = 71 (closed 10/07). Mean age 51, 68% white, 26% African American. 87% received prior adjuvant chemo, 54% prior chemo for MBC (24% > 1 prior). Arm 1: PR 6% (2 pts, > 40 weeks), stable disease (SD) 4%, and clinical benefit (CB=PR or SD > 6mos) 10%. Arm 2: RR 18% (13 pts), SD 9% (6), and CB 27% (19). PR did not appear to differ by line of therapy: 14% 1st-line, 31% 2nd-line, 17% 3rd-line. Most pts progressed rapidly; median PFS was 2.0 months. The regimen was tolerable, grade 3 toxicity occurring in > 5% pts were: Arm 1 - rash only (10% pts); Arm 2 - rash (6%), fatigue (6%), and N/V (6%). Two grade 4 infusion reactions occurred in Arm 2. Biopsies from 16 mets confirmed subtype: basal-like (13), claudin-low (2), HER2+/ER- (1). Preliminary pharmacodynamics on paired biopsies (before/after 1–2 weeks therapy) in 9 pts reveal that 7 had gene expression evidence of activity across the EGFR pathway: 2 decreased with treatment (1PR, 1SD); 5 had no change or increased activity with treatment (1SD, 4 PD). Final response rates and further correlative endpoints will be presented. Conclusions: C alone was well tolerated but has low activity in TN MBC. C+P has 18% RR and 27% CB. Many pts progressed rapidly, consistent with the aggressive behavior of this tumor subtype. Serial biopsies offer insight into EGFR pathway modulation by therapy. Translational studies confirming molecular subtype, identifying biologic effects of EGFR inhibition and platinum, evaluating circulating tumor cells, and studying the BRCA1 pathway are ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb