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Neoadjuvant treatment in patients with high-risk early breast cancer

Conference
ESMO 2020

Both GeparOcto and IMpassion031 evaluated neoadjuvant treatment in patients with high-risk early breast cancer [1-3]. Atezolizumab significantly improved pathologic complete response (pCR) rates.

GeparOcto randomised 961 patients with high-risk early breast cancer (TNBC, HER2-positive, or ER-positive/HER2-negative) to receive either 9 cycles of sequential neoadjuvant treatment with intense dose-dense epirubicin, paclitaxel, cyclophosphamide (iddEPC) or weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin for 18 weeks (PM). Patients with TNBC in the PM arm also received weekly carboplatin (Cb); in both treatment arms patients with HER2-positive disease received trastuzumab/pertuzumab.

The primary endpoint, pathological complete response (pCR), did not differ between both arms in the whole cohort as well as in subgroups [1]. After a median follow-up of 47 months, there were no overall differences in invasive disease-free survival (iDFS) and overall survival (OS) between both arms [2]. However, in patients with ER-positive/HER2-negative breast cancer, iDFS was significantly longer for iddEPC versus PM (4-year iDFS 62.5% vs 77.9%; HR 2.11; P=0.0284), translating into a 4-year OS benefit of 80.1% versus 94.7% (HR 3.26; P=0.0388).

In IMpassion031, a total of 333 untreated patients with early TNBC (invasive stage II-III, tumour size > 2 cm) were randomised to neoadjuvant treatment with atezolizumab (840 mg every two weeks) plus nab-paclitaxel (125 mg/m2 every week) for 12 weeks, followed by atezolizumab (840 mg every 2 weeks) plus doxorubicin (60 mg/m2 every 2 weeks)/cyclophosphamide (600 mg/m2 every 2 weeks) for 8 weeks, versus placebo plus doxorubicin/cyclophosphamide followed by surgery. After surgery, pCR (ypT0/isN0) was assessed in all patients. pCR was seen in 57.6% of patients in the atezolizumab-chemo arm and in 41.1% of patients in the placebo-chemo arm (Δ16.5%; P=0.0044) [3]. Median event-free survival, DFS, and OS were not reached in either arm although the trends supported a benefit for atezolizumab (HR 0.76, 0.74, and 0.69, respectively).

  1. Schneeweiss A, et al. Eur J Cancer 2019;106:181-192.
  2. Schneeweiss A, et al. Survival analysis of the randomized phase III GeparOcto trial comparing neoadjuvant chemotherapy (NACT) of iddEPC versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer, TNBC) (PM(Cb)) for patients (pts) with high-risk early breast cancer (BC). ESMO 2020 Virtual Meeting, abstract 160O.
  3. Harbeck N, et al. IMpassion031: Results from a phase III study of neoadjuvant (neoadj) atezolizumab + chemotherapy in early triple-negative breast cancer (TNBC). ESMO 2020 Virtual Meeting, abstract LBA11.


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