532 Background: NOAH (NeOAdjuvant Herceptin) is a Phase III trial of neoadjuvant trastuzumab; H) in combination with chemotherapy in patients (pts) with HER2-positive locally advanced breast cancer (LABC). Methods: 228 pts with centrally confirmed HER2-positive (IHC 3+ or FISH+) LABC received 3 cycles of doxorubicin-paclitaxel (AT: A 60 mg/m2, T 150 mg/m2 q3w), 4 cycles of T (175 mg/m2 q3w) and 3 cycles of cyclophosphamide/methotrexate/5-fluorouracil (CMF: C 600 mg/m2, M 40 mg/m2, F 600 mg/m2 q4w) on days 1 and 8, with (n=115) or without (n=113) concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. Pts with HER2- negative disease (IHC 0/1+; n=99) were treated in parallel with AT/T/CMF. The primary end point was event-free survival (EFS); secondary end points included overall response rate (ORR), pathological complete response (pCR) rate and safety. Results: Baseline characteristics were well balanced for randomised pts. Median tumour size was 5.5 cm (range 1.5–20.0). Inflammatory breast cancer (IBC) was present in 40% of HER2-positive vs 14% of HER2-negative tumours, while 35% vs 65%, respectively, were hormone receptor positive. Left ventricular ejection fraction (LVEF) at baseline was similar in all 3 groups. Adding H to AT/T/CMF improved ORR (81% vs 73%; p=0.18) and significantly increased pCR rate (43% vs 23%; p=0.002). This response pattern was also seen in IBC pts. ORR (66%) and pCR rate (17%) for pts with HER2-negative disease were similar to pt responses in the HER2-positive group who did not receive H. The most common serious adverse event was febrile neutropenia (8% with H vs 4% without). Only 11% of pts receiving H had absolute LVEF decreases of =10% and 1 pt treated with H experienced a cardiac event with an LVEF value of <45%. One pt with HER2-negative disease died after surgery due to pulmonary embolism. Conclusions: Neoadjuvant H plus AT/CMF-containing chemotherapy significantly improved the pCR rate of LABC vs chemotherapy alone. Treatment was well tolerated with acceptable cardiac safety. Follow-up is ongoing and EFS is maturing. [Table: see text]
154P Five-year follow-up of the phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in patients with HER2 positive early or locally advanced breast cancer
