Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC).

Abstract

511 Background: Retrospective data suggest that patients (pts) with small HER2+ cancers have more than just minimal risk of disease recurrence. The APT trial was designed to address treatment for such pts. We have previously reported 3-yr disease-free survival (DFS) and here we provide an updated analysis with 7-yr DFS. Methods: APT is a single arm multicenter, phase II study of TH. Pts with HER2+ BC (IHC 3+ and/or FISH ratio > 2.0) with negative nodes (a single axillary lymph node micrometastasis was allowed) and tumor size < 3 cm were eligible. Pts received T (80 mg/m2) with H x 12 weekly (w), followed by H (weekly or q3w) x 39w. The primary endpoint was DFS. Recurrence Free Interval (RFI), Breast Cancer Specific Survival (BCSS), and overall survival (OS) were also analyzed. Intrinsic subtyping by PAM50 was performed on the nCounter Analysis system on archival tissue. Results: 410 pts were enrolled from September 2007 to September 2010 and 406 began protocol therapy. 67% had hormone-receptor (HR)+ tumors. Distribution by tumor size: 2% T1mi; 17% T1a; 30% T1b; 42% T1c, and 9% T2 ≤ 3 cm. 6 pts had a nodal micrometastasis. With a median follow-up of 6.5 yrs, there were 23 DFS events observed: 4 (1.0%) distant recurrences, 5 local/regional recurrences (1.2%), 6 new contralateral BC (1.5%), and 8 deaths without documented recurrence (2.0%). The 7-yr DFS was 93.3% (95% CI 90.4-96.2); 7-yr DFS for HR+ pts was 94.6% (95% CI 91.8-97.5) and for HR- pts was 90.7% (95% CI 84.6-97.2). 7-yr RFI was 97.5% (95% CI 95.9-99.1); 7-year BCSS is 98.6% (95% CI 97.0-100); and 7-yr OS was 95.0% (95% CI 92.4-97.7). Ongoing PAM50 testing (n = 227 pts) identified 142 (63%) HER2-enriched; 22 (10%) luminal A, 26 (11%) luminal B, and 20 (9%) basal-like; 17 samples had a poor quality assay. Additional testing and associations with clinical outcomes will be presented at the meeting. Conclusions: These data suggest that TH as adjuvant therapy for node-negative HER2+ BC is associated with few recurrences and only 4 distant recurrences with longer follow-up. Based on these data, if chemotherapy/trastuzumab is given to a pt with stage I HER2+ breast cancer, the TH regimen should be considered a standard treatment. Clinical trial information: NCT00542451.