Abstract S1-04: A phase II study of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC)

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Abstract Background: Four large randomized phase III trials have reported significant improvements in disease-free (DFS) and overall survival for H administered with adjuvant polychemotherapy for HER2-positive high-risk BC. With the success of HER2-targeting, limiting chemotherapy is both reasonable and feasible, particularly for smaller, node-negative tumors. However data are limited. Methods: APT is a single arm three-stage, multicenter, phase II study of TH. Patients (pts) with HER2-positive BC (IHC 3 + and/or FISH amplified at > 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 (4 mg/kg load ®2 mg/kg) x 12 weekly (w), followed by H x 39 w (2 mg/kg weekly or 6 mg/kg q 3 w). The primary endpoint was DFS. DFS events included invasive local, regional or distant recurrence, contralateral invasive breast cancer and death from any cause. The study had 95% power to distinguish between 3-year failure rates of 9.2% vs. 5% using a Poisson model based on the total patient-years of follow-up (PYFU). Planned interim analyses were designed to stop early for futility at 225 and 800 PYFU, and the regimen would be deemed worthy of further study with <40 failures after 1600 PYFU. All pts who began protocol therapy were included in the analyses. Results: 410 pts were enrolled from September 2007 to September 2010 and 406 began protocol therapy. The median age was 55 (range 24-85 years). Sixty-three percent had ER+ tumors. Three percent of tumors were T1mi; T1a; 20% T1b; 41% T1c, and 9% T2 ≤ 3cm. Six pts had a nodal micrometastasis. 356 pts (88%) completed all 52 wks of therapy, with 24 and 6 pts discontinuing due to protocol-specified or other toxicities, respectively. 358 (89%) completed all 12 weeks of combined TH therapy. The most common grade 3/4 toxicities included: neuropathy (4%), neutropenia (4%), transaminitis (3%), leukopenia (2%), fatigue (2%), and hypersensitivity reactions (2%). Reversible symptomatic CHF (grade 3 left ventricular systolic dysfunction) occurred in 2 patients (0.5%). Because of the limited number of events, the Data Safety Monitoring Board approved release of study results with 1316 PYFU and a median follow-up of 3.2 years. A total of 8 DFS events have been observed: 2 pts with metastatic disease, 2 with ipsilateral axillary recurrences, 3 with new contralateral BC (all HER2-), and 1 patient who died after diagnosis of primary ovarian cancer. Conclusion: This represents the first report of TH as adjuvant therapy for node-negative HER2-positive BC. The regimen appears well tolerated and few recurrences have been observed in the study population to date. An updated analysis of efficacy, including estimates of 3-year DFS, will be presented in December when a total of 1520 PYFU in this cohort is anticipated. Based on these early data, the TH regimen may be an acceptable treatment approach for low risk HER2-positive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S1-04.