Background Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is noninferior to the standard 12-month treatment regarding disease-free survival. Methods This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006-007018-39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140).
e12108 Background: Neoadjuvant (NA) HER2 blockade with trastuzumab (T) and pertuzumab (P) results in pathological complete response (pCR) rates of 39% to 62%. Diarrhoea is reported in up to 73% of cases. No real-world studies have explored the efficacy and toxicity of this treatment. This study aimed to determine the efficacy and toxicity of NA T-P and CT within a routine NHS clinical practice in the UK. Methods: HER2+ BC patients given NA T-P (accessed via the Cancer Drug Fund) between Oct2016-Jan 2018 at Clatterbridge Cancer Centre NHS Foundation Trust were retrospectively identified. Clinico-pathological information, treatment data, nurse led toxicity and echocardiography were reviewed. Data lock: 30th January 2019. Final pathological response data is presented. Results: 78 female patients were identified with a median age of 50 years (IQR: 44.4-60.2). Diagnosis: median tumour size 30mm (IQR 23.0-47.5mm), 62% (48/78) LN+ & 71% ER+. CT regimens: 81% (63/78) given FEC-DHP; of these 19 (30%) switched to weekly paclitaxel (wP) or nab-paclitaxel; 5% (4/78) AC/EC-DHP; 9% (8/78) TCHP of which 1 (13%) switched to wP. All patients underwent definitive surgery: 50% (39/78) mastectomy & 50% (39/78) WLE. 44% (35/78) axillary node clearance (ANC) & 56% (43/78) sentinel node biopsy (4 prior to NA therapy). 91% (32/35) undergoing ANC were LN+ at diagnosis, of which 66% (21/32) were LN- at surgery. pCR rate (ypT0/is, N0) was 47% (37/78), pCR by HR: ER+ 42% (23/55) & ER- 61% (14/23). pCR for 20 cases switched to wP was 60% (12/20). 6% (5/78) achieved pCR in the breast alone (in these LN status ITCx1, micrometsx3 & macrometsx1). Median size of the 46% (36/78) with residual breast tumour was 14.5mm (1-65mm). Outcome: Median follow up 68 weeks with one local and one distant recurrence occurring but no deaths. Toxicity: Ejection fraction did not decline beyond 10% of baseline in any patients. Diarrhoea occurred in 74% of cases, and CTCAE grade 3-4 toxicity occurring in >2% of patients: diarrhoea, fatigue, and infection. Conclusions: This data confirms 1) the real world efficacy of NA T-P 2) a significant number of LN+ patients become LN- and measures to avoid ANC are needed 3) switching to NA wP is not uncommon and may be associated with a higher pCR 4) diarrhoea rates reflect the literature and measures to mitigate it are needed. Updated outcomes will be presented.
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