Potential Predictive Markers of Benefit from Cetuximab in Metastatic Breast Cancer: An Analysis of Two Randomized Phase 2 Trials.

作者：Lisa A. Carey, Joyce O’Shaughnessy, Joyce O’Shaughnessy, KA Hoadley, Shirin Khambata‐Ford, Christine E. Horak, Xu Li, M. Awad, Daniel Brickman, Simon Müller, Jessica Donato, L. Asmar, I. Stiljeman, Mark Ebbert, Philip S. Bernard, C. Perou · 发表于：Cancer Research · 年份：2009 · DOI：10.1158/0008-5472.sabcs-09-2014 · 被引用次数：19 · 研究领域：Advanced Breast Cancer Therapies、Cancer Treatment and Pharmacology、Colorectal Cancer Treatments and Studies

Abstract Background: Two randomized phase 2 studies investigated the efficacy of cetuximab (C), a mAb directed against EGFR, in metastatic breast cancer (MBC) patients (pts). Trial 1 (T1) compared the response rates in triple negative breast cancer (TNBC) pts on C vs. C plus carboplatin (Cb), and, in Trial 2 (T2), both TNBC and ER+/HER2- pt subsets were assessed for response to irinotecan (I) plus Cb vs. C plus ICb. In T2, TNBC pts showed an improved objective response rate with C treatment, while ER+/HER2- pts did not. Formalin-fixed paraffin-embedded (FFPE) primary breast cancer tissues were available from pts on both trials for retrospective analyses of potential predictive biomarkers of C treatment.Material and Methods: In T1 and T2, 64 and 68 pts, respectively, had tissue for qRT-PCR analyses of genes important for breast cancer subtyping (PAM50) and EGFR pathway-related genes. PAM50 analysis showed that 76 of the 132 pts on the 2 trials had basal-like breast cancer (BBC). In T1, 43 of the 64 (67%) TNBC pts had BBC, 3 were HER2-enriched, 5 were luminal A and 13 were normal-like breast cancer. In this trial, 10 of 64 pts (16%) had progression-free survival (PFS) duration ≥6 mo (long remitters [LRs]) with 4 pts having PFS ≥12 mo; 6 of the 10 LRs had BBC. In T2, 22 of 68 pts were LRs (32%) (11 of 22 received C) and 9 pts had PFS ≥12 mo (5 received C). 11 of the 37 BBC pts in T2 had PFS ≥6 mo (5 received C) and 4 of 11 had PFS ≥12 mo (2 received C). The following EGFR pathwa...