Pathologic Complete Response with Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel with Trastuzumab and Pertuzumab in Patients with HER2‐Positive Early Stage Breast Cancer: A Single Center Experience

In this neoadjuvant trial (TRIO-US B07), participants with early-stage HER2-positive breast cancer (N=128) were randomized to receive trastuzumab (T), lapatinib (L), or both (TL) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. We observed similar pathologic complete response (pCR) rates between T and TL, and a lower pCR rate with L. Higher-level amplification of HER2 and hormone receptor-negative status were associated with a higher pCR rate. Higher pre-treatment immune infiltrate trended toward higher pCR rate in T-treated groups, and greater HR expression correlated with lower immune infiltrate. Large shifts in tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.

Download Full-text

A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.518 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 518-518 ◽

Cited By ~ 7

Author(s):

Andreas Schneeweiss ◽

Volker Moebus ◽

Hans Tesch ◽

Claus Hanusch ◽

Carsten Denkert ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Early Stage ◽

Pathologic Complete Response ◽

Neoadjuvant Treatment ◽

Complete Response ◽

Primary Objective ◽

Early Stage Breast Cancer ◽

Phase Iii ◽

Luminal B

518 Background: The sequential use of intense does-dense (idd) epirubicin, paclitaxel, cyclophosphamide (EPC) and weekly paclitaxel/liposomal doxorubicin (+/- carboplatin (Cb) in triple negative breast cancer (TNBC) (PM(Cb)) are considered highly efficient regimens for high-risk early stage breast cancer (BC). Methods: GeparOcto (NCT02125344) patients (pts) received 18 weeks (wks) either EPC (3x E 150mg/m² q2w followed by 3x P225 mg/m² q2w followed by 3x C 2000mg/m² q2) or PM(Cb) (12x P 80mg/m² plus M 20 mg/m² q1w, plus Cb AUC 1.5 q1w in TNBC). For HER2+ BC trastuzumab 6 (8) mg/kg q3w and pertuzumab 420 (840) mg q3w cycles were given concomitantly with P and C. Pts with histologically confirmed, cT1c - cT4a-d BC and central receptor assessment were included. Pts with HER2+ or TNBC were eligible irrespective of nodal status, luminal B-like tumours only if pN+. Primary objective compared pathologic complete response (pCR) rates (ypT0/is ypN0). Sample size calculations assumed a pCR rate of 50% for EPC and 60% for PM(Cb), requiring 950 pts to show superiority of PM(Cb). Secondary objectives compared pCR rates within the stratified subgroups (BC subtype, HER2+ vs HER2- HR+ vs HER2- HR-), amongst others. Results: 961 pts were recruited between 12/2014 and 05/2016, 945 started treatment. Median age was 48 years, 4% T3, 2% T4d, 46% N+, 82% ductal invasive, 66% G3 tumors; 40% were HER2+, 43% TNBC. 347 pts reported SAEs (176 EPC/171 PM(Cb)) and 2 pts died. 35 pneumonias (2 EPC vs 33 PM(Cb)) and 18 pneumonitis (3 EPC vs 15 PM(Cb)) were reported. 16.4% pts with EPC and 33.8% with PM(Cb) discontinued treatment (p<0.001), mainly due to AEs (47 EPC vs 113 PM(Cb)). Mean treatment duration was 17 wks with EPC and 16 wks with PM(Cb). pCR rate was 48.3% with EPC and 47.6% with PM(Cb)(OR 0.97 (95%CI 0.75-1.25), p=0.876). pCR rate in TNBC was 48.5% with EPC and 51.7% with PM(Cb); in HER2+ 62.0% vs 57.4% and in Luminal B 14.1% vs 14.6%. Conclusions: In high-risk early stage breast cancer pts pCR rates of idd EPC compared to weekly PM(Cb) were not significantly different. PM(Cb) appeared to be less feasible. Clinical trial information: NCT02125344.

Download Full-text