Citation: Cancer Research. 2019, 79(4)
Author: Hall B.; Bhojwani A.; Innes H.; Ahmed E.; Cliff J.; Malik Z.; O'Hagan J.; Tolan S.; Hall A.; Hayat K.; Errington D.; Alam F.; Thorp N.; Flint H.; Law A.; Wong H.; O'Reilly S.; Jackson R.; Cicconi S.; Palmieri C.
Abstract: Background: Studies of neoadjuvant (NA) dual HER2 blockade with trastuzumab (T) and pertuzumab (P) in combination with chemotherapy (CT) for early breast cancer (BC) have reported pathological complete response (pCR) rates of 39 to 62%. These studies also report manageable toxicity with diarrhoea reported in up to 73% of cases. To date no real-world studies have explored the efficacy and toxicity of this treatment. The objective of this study was to describe the medical and surgical management of women treated with neoadjuvant T-P in combination with CT (NAT-P-CT). As well as to determine the efficacy toxicity of NAT-P-CT in the context of a routine UK NHS clinical practice. <br/>Method(s): Patients with HER2+ BC treated neoadjuvantly with T-P accessed via the NHS England Cancer Drug Fund (CDF) at the Clatterbridge Cancer Centre NHS Foundation Trust between October 2016 and January 2018 were retrospectively identified. Clinico-pathological information, treatment data, nurse led toxicity review and echocardiographic were reviewed. Data lock was 19th June 2018. <br/>Result(s): 78 female patients were identified with a median age of 50 years (IQR: 44.4-60.2). At diagnosis: median tumour size 30mm (23.0-47.5mm), 62% (48/78) were LN positive & 56% (44/78) ER+. CT regimens: 81% (63/78) FEC-DHP of these 30% (19/63) switched to weekly paclitaxel (wP). or nab-paclitaxel; 5% (4/78); AC/EC-DHP; 9% (8/78) TCHP with 13% (1/8) switched to wP. At time of analysis, 88% (69/78) had undergone definitive surgery. Surgical details: Breast: 52% (36/69) mastectomy & 48% (33/69) WLE, Axillary management: 51% (35/69) axillary dissection (Ax Dx) & 49% (34/69) sentinel node biopsy (4 performed prior to NA treatment). 91% (32/35) of those undergoing Ax Dx were LN+ at presentation, of these 59% (19/32) had no evidence of axillary involvement at surgery. pCR rate (ypTO/is, NO) was 46% (32/69) [pCR by HR: ER+ 43% (21/49) & ER-55% (11/20]. pCR for 20 patients switched to wP was 60% (12/20). 7% (5/69) achieved pCR in the breast alone (in these LN status ITCx1, micrometsx3 & macrometsx1). Of the 54% (37/69) with residual breast tumour median size was 13mm (1-22mm). Toxicity Data: Ejection fraction (EF) did not decline beyond 10% of baseline in any patients. Diarrhoea (any grade) occurred in 74% of cases, and CTCAE grade 3-4 toxicity occurring in >2% of patients: diarrhoea, fatigue, and infection. Updated analysis regarding pCR rate and toxicity, as well as initial outcome data will be presented.
Conclusion(s): These results (1) confirm the efficacy of NA T-P in a real world population; (2) support the use of NA wP; (3) indicate significant proportion of patients axilla are downstaged & (4) reveal diarrhoea rates in keeping with the literature. Currently, NHS England rules do not allow wP to be used routinely in NA setting with T-P this should be reviewed in light of these data and those of the BERENICE study. Measures to identify patients who can avoid axillary dissection as well as to mitigate diarrhoea should be considered.
