Real-world evidence regarding the efficacy and toxicity of neoadjuvant trastuzumab and pertuzumab in the management of HER2-positive early-breast cancer.

Abstract

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.

Efficacy and safety of neoadjuvant pertuzumab plus trastuzumab in combination with chemotherapy regimen in Chinese patients with HER2-positive early breast cancer: a real-world retrospective multi-center cohort study

“…The pCR rate of our realworld study was 46.8% which is similar to that reported in previous clinical trials (39.3-68%) evaluating neoadjuvant pertuzumab plus trastuzumab dual anti-HER2 therapy in early or locally advanced HER2-positive BC (10,20,22,28). The pCR rate in this context was also concordant with other real-world studies of neoadjuvant treatment with double HER2 blockade in routine clinical regimens of HER2-positive early or LABC which confirmed the notable pCR benefit of neoadjuvant pertuzumab plus trastuzumab in previous randomized clinical trials (29)(30)(31)(32).…”

Neoadjuvant chemotherapy and HER2 dual blockade including biosimilar trastuzumab (SB3) for HER2-positive early breast cancer: Population based real world data from the Danish Breast Cancer Group (DBCG)

“…Other groups have examined dual blockade in a real-world setting. A 2018 study among 78 women with HER2-positive EBC found an overall pCR rate of 47% and a 2019 study among 166 patients found a pCR rate of 55% [ 31 , 32 ]. Neither studies used biosimilar trastuzumab.…”