0000000000001048
AUTHOR
Pinuccia Valagussa
Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort.
Summary Background In our randomised, controlled, phase 3 trial NeOAdjuvant Herceptin (NOAH) trial in women with HER2-positive locally advanced or inflammatory breast cancer, neoadjuvant trastuzumab significantly improved pathological complete response rate and event-free survival. We report updated results from our primary analysis to establish the long-term benefit of trastuzumab-containing neoadjuvant therapy. Methods We did this multicentre, open-label, randomised trial in women with HER2-positive locally advanced or inflammatory breast cancer. Participants were randomly assigned (1:1), by computer program with a minimisation technique, to receive neoadjuvant chemotherapy alone or with …
Follow-up results of NOAH, a randomized phase III trial evaluating neoadjuvant chemotherapy with trastuzumab (CT+H) followed by adjuvant H versus CT alone, in patients with HER2-positive locally advanced breast cancer.
503 Background: The monoclonal antibody trastuzumab (H) has been shown to improve event-free survival (EFS) and pathologic complete response (pCR) in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without one year of trastuzumab in the primary analysis of the NOAH study (Gianni L, Lancet 2010). Updated EFS and overall survival (OS) results are now presented. Methods: In this international, multicenter, open-label, randomized phase III trial patients with locally advanced or inflammatory breast cancer were randomized 1:1 to receive CT+H followed by adjuvant H versus CT alone. A parallel cohort of 99 comparable patients w…
Five-year analysis of the phase II NeoSphere trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P).
505 Background: InNeoSphere, four cycles of T+D, P+T+D, P+T, or P+D, followed by surgery and adjuvant chemotherapy plus conventional T, were evaluated in 417 women with locally advanced, inflammato...
Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy.
Abstract Purpose: The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin → CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel → CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate. Methods: A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C. Results: Grade 3 or 4 National Cancer Insti…
Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial
Summary Background Studies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting. Methods In this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg…
5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial.
Summary Background In the primary analysis of the NeoSphere trial, patients given neoadjuvant pertuzumab, trastuzumab, and docetaxel showed a significantly improved pathological complete response compared with those given trastuzumab and docetaxel after surgery. Here, we report 5-year progression-free survival, disease-free survival, and safety. Methods In this multicentre, open-label, phase 2 randomised trial in hospitals and medical clinics, treatment-naive adults with locally advanced, inflammatory, or early-stage HER2-positive breast cancer were randomly assigned (1:1:1:1) to receive four neoadjuvant cycles of trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus do…
Proliferation-, estrogen-, and T-cell-related metagenes to predict outcome after adjuvant/neoadjuvant chemotherapy for operable breast cancer in the ECTO trial.
1014 Background: Predicting recurrence in operable breast cancer (BC) despite optimal chemotherapy would be relevant to new drug development and tailored treatments. Methods: A large series (n=3,154) of public Affymetrix gene-expression profiles (GEP) was used to define prognostic/predictive metagenes in different BC subtypes. In ER+/HER2- a proliferation and an ER-related metagene were combined to predict low, intermediate and high risk of recurrence. In TN and in HER2+ a T cell metagene was used to predict low, intermediate and high risk (higher expression associated with lower risk). The metagenes were validated in patients enrolled in the phase III ECTO trial (Gianni L. JCO 2009) and t…
Freedom from progression (FFP) by adding paclitaxel (T) to doxorubicin (A) followed by CMF as adjuvant or primary systemic therapy: 10-yr results of a randomized phase III European Cooperative Trial in Operable Breast Cancer (ECTO).
537 Background: At the time the ECTO was designed in 1996, taxanes were only indicated for patients with metastatic breast cancer. However, paclitaxel and docetaxel were still to be tested in the adjuvant setting. In addition there was relatively scarce information on the comparative efficacy of neoadjuvant and adjuvant regimens. The ECTO trial was designed to evaluate the addition of paclitaxel to an anthracycline-based adjuvant regimen and to compare this combination with the same regimen given as primary systemic (neoadjuvant) therapy. Methods: A total of 1,355 women with operable breast cancer were randomized to one of three treatments: 1) surgery followed by adjuvant single agent doxo…