Randomized Study Comparing Efficacy/Toxicity Of Monotherapy Trastuzumab Followed By Monotherapy Docetaxel At Progression, And Combination Trastuzumab/Docetaxel As First-Line Chemotherapy In Her2-Neu Positive, Metastatic Breast Cancer (Mbc) (Hertax Study)

1014 Background: Treatment with trastuzumab and chemotherapy has improved the outcome of HER2-positive MBC. It is unknown what the outcome and toxicity is of monotherapy trastuzumab, followed by chemotherapy at progression, as compared to the combination of chemotherapy/trastuzumab. Methods: HER2-positive MBC pts., being eligible for first line chemotherapy were randomised between combination treatment docetaxel (TAX) (100 mg/m2, q3wks)/trastuzumab (HER) (loading dose 4mg/kg, whereafter weekly 2mg/kg) (arm A) or monotherapy HER, followed upon progression by TAX (similar doses as arm A) (arm B). Further in- /exclusion criteria were adjuvant non-taxoid chemotherapy allowed, previous HER treatment not; normal ejection fraction (EF), adequate liver/renal functions and bone marrow reserve. Primary endpoint was PFS, secondary endpoints: response rate (RR), overall survival (OS) and toxicities. Kaplan-Meier curve was tested by log-rank test, RR by Pearson χ2-test. Results: Of the 101 randomly selected patients, 2 were ineligible. Patient characteristics in arms A/B were not significantly (NS) different, being: median age 52/53 yrs (range 32–74); ER/PgR positive 47/47%; adjuvant chemo-/hormone therapy in 46/25% and 42/33%, respectively; prior hormone therapy for MBC in 37/36%. Objective RRs were 57% and 34% (p=0.03). PFS in arm A was 9.1 mo, while PFS on HER was 3.9 mo (p=0.0001), and after consecutive TAX 9.8 mo (arm B) (p=0.22). OS data is being analysed, and will be presented. Grade 3/4 neurosensory toxicity was only seen in arm A (6%). Other grade 3/4 toxicity was NS different (pulmonary complaints (9%), fatigue (8%), other ≤5%). Serious adverse events more frequently occurred in arm A (25/4), 2 toxic deaths in arm A, neutropenic fever 27/16%. LVEF decline >20% occurred in 16/15%. Conclusions: Monotherapy HER followed by monotherapy TAX yields a similar PFS as compared to combination therapy HER/TAX, and is associated with less grade 3/4 toxicity. Cardiac toxicity is NS different between both treatment modalities. Delaying cytotoxic therapy by using monotherapy HER may be a treatment option for particular patients. No significant financial relationships to disclose.