PD07-03: Phase II Trial of Adjuvant TC (Docetaxel/Cyclophosphamide) Plus Trastuzumab (HER TC) in HER2−Positive Early Stage Breast Cancer Patients.
Authors: Jones S , Collea R , Paul D , Oratz R , Sedlacek S , Favret AM , Gore II , Lindquist DL , Holmes FA , Allison MAK , Steinberg MS , Stokoe C , Portillo RM , Crockett M , Wang Y , Asmar L , Robert N , O'Shaughnessy J 
Published: June 2012

Abstract
Introduction: TC is an effective adjuvant chemotherapy regimen in early stage breast cancer (ESBC) patients. Jones et al (J Clin Oncol 2009 Mar 10;27(3): 1177–1183) demonstrated a significantly superior 5-year DFS and OS for TC compared to AC. Because TC was superior to AC in a subset analysis of HER2+ breast cancer treated without trastuzumab, we tested TC in combination with 1 year of trastuzumab in lower risk HER2+ ESBC, predominately node negative disease.
Methods: This was an open-label, phase II study of TC+H in HER2+ patients based on HER2 overexpression determined at the local level. Tissue was collected for central review of HER2 and TOP2A status. There was no lower limit of tumor size for lymph node negative cancers. Every 21 days, patients received docetaxel (T) 75mg/m2 IV, plus cyclophosphamide (C) 600mg/m2 IV, plus weekly trastuzumab (H) 4mg/kg IV (loading dose) and 2mg/kg IV thereafter for a total of 4 cycles. After 4 cycles of TC+H, patients continued on H for a total of 1 year. Appropriate patients received radiotherapy. Cardiotoxicity (decreased left ventricular ejection faction) was assessed by MUGA or ECHO at baseline, at completion of TC+H, and then at 3-month intervals until completion of trastuzumab treatment. The primary endpoint was DFS at 2 years with continued follow-up for 3 years. Secondary endpoints were OS and safety.
Results: 486 patients received treatment, and 397(82%) completed a full year of H. Median age was 55 years(range: 24–75.8), ECOG PS 0=426(87.7%) and 1=60(12.3%); 280(57.6%) were Stage 1, 200(41.2%) were Stage II, and 6(1.2%) were Stage III. Disease-free survival and OS at 2 and 3 years are listed in the table below according to various features.

The most common Grade 3/4 toxicities were neutropenia (47.1%) and febrile neutropenia (6.2%). There were 5 deaths: 1 due to PD, 1 aspiration, and 1 respiratory distress syndrome (possibly related to treatment), 1 cardiopulmonary arrest, and 1 unknown. There were 13 cases of recurrent breast cancer (local 5, or local/distant 8). Cardiac dysfunction occurred in 28(5.8%) patients, with 12(2.5%) being Grade 1, 14(2.9%) Grade 2, and 2(0.4%) grades 3/4. Sixteen patients had to stop H due to cardiac dysfunction with H. Central assessment of TOP2A status was performed by FISH in 90% of cases: TOP2A-amplified (42%), deleted (27%), and normal (31%). However TOP2A status had no effect on outcome.
Conclusions: 1) The HER TC regimen was evaluated in 486 patients with HER2 overexpressed ESBC and found to be effective at the primary endpoint of 2 years. 2) Efficacy was demonstrated in node negative cancer including 94 cancers &lt;1 cm. 3) Toxicity was acceptable with a low rate of cardiac dysfunction, mainly reversible. 4) The HER TC regimen is an option for patients with lower risk HER2 overexpressing ESBC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD07-03.