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Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication Vrije Universiteit Brussel

D Miles, E Ciruelos, A Schneeweiss, F Puglisi, T Peretz-Yablonski, M. Campone, I Bondarenko, Z Nowecki, H Errihani, S Paluch-Shimon, et al.

BACKGROUND: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined ...

Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy Vrije Universiteit Brussel KU Leuven

Tineke Vandenbroucke, Magali Verheecke, Mathilde van Gerwen, Kristel Van Calsteren, Michael J Halaska, Monica Fumagalli, Robert Fruscio, Amarendra Gandhi, Margreet Veening, Lieven Lagae, et al.

BACKGROUND: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce.

METHODS: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive ...

Emerging drugs targeting human epidermal growth factor receptor 2 (HER2) in the treatment of breast cancer Vrije Universiteit Brussel

Gil Awada, Andrea Gombos, Philippe Aftimos, Ahmad Awada

INTRODUCTION: Human epidermal growth factor 2 (HER2) overexpression is present in 20% of breast cancer patients. It is associated with more aggressive disease and worse clinical outcome. New drugs are thus needed. Approved and future treatments will be discussed in this review.

AREAS COVERED: The monoclonal antibodies trastuzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib and the antibody-drug conjugate trastuzmab ...

Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study University of Antwerp Ghent University

Udai Banerji, Carla M.L. van Herpen, Cristina Saura, Fiona Thistiethwaite, Simon Lord, Victor Moreno, Iain R. Macpherson, Valentina Boni, Christian Rolfo, Elisabeth G.E. de Vries, et al.
Background Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate comprised of trastuzumab covalently bound to a linker drug containing duocarmycin. Preclinical studies showed promising antitumour activity in various models. In this first-in-human study, we assessed the safety and activity of trastuzumab duocarmazine in patients with advanced solid tumours. Methods We did a phase 1 dose-escalation and dose-expansion study. ...

Neratinib, an irreversible ErbB receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer KU Leuven

Robert Paridaens
Purpose: Neratinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor. The efficacy and safety of neratinib were evaluated in two cohorts of patients with advanced ErbB2-positive breast cancer - those with and those without prior trastuzumab treatment - in an open-label, multicenter, phase II trial. Patients and methods: Patients in the two cohorts (prior trastuzumab, n = 66; no prior trastuzumab, n = 70) received oral ...

Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial KU Leuven

Eric Van Cutsem
BACKGROUND: Evidence for the efficacy of combined PD-1 and HER2 blockade with chemotherapy on progression-free and overall survival in HER2-positive gastro-oesophageal cancer is scarce. The first interim analysis of the randomised, phase 3 KEYNOTE-811 study showed a superior objective response with pembrolizumab compared with placebo when added to trastuzumab plus fluoropyrimidine and platinum-based chemotherapy. Here, we report results from ...

Multicenter Phase III Randomized Trial Comparing Docetaxel and Trastuzumab With Docetaxel, Carboplatin, and Trastuzumab As First-Line Chemotherapy for Patients With HER2-Gene-Amplified Metastatic Breast Cancer (BCIRG 007 Study): Two Highly Active Therap.. Hasselt University

Vicente Valero, John Forbes, Mark D. Pegram, Tadeusz Pienkowski, Wolfgang Eiermann, Gunter von Minckwitz, Henri Roche, Miguel Martin, John Crown, John R. Mackey, et al.
Purpose Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC. Patients and Methods Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m(2)) or ...

Neoadjuvant capecitabine and docetaxel (plus trastuzumab): an effective non-anthracycline-based chemotherapy regimen for patients with locally advanced breast cancer KU Leuven

Hans Wildiers, Patrick Neven, Rose Christiaens, Frédéric Amant, Caroline Weltens, Ann Smeets, Erik Van Limbergen, Liza Van Eenoo, Robert Paridaens
Background: To evaluate capecitabine–docetaxel (XT), with trastuzumab (H) in human epidermal growth factor receptor 2 (HER2)-positive disease, in inoperable locally advanced breast cancer (LABC). Patients and methods: Patients received up to six neoadjuvant 21-day cycles of capecitabine 900 mg/m2 twice daily, days 1–14, plus docetaxel 36 mg/m2, days 1 and 8. Patients with HER2-positive disease also received trastuzumab 6 mg/kg every 3 weeks. The ...

A phase Ib study of pictilisib (GDC-0941) in combination with paclitaxel, with and without bevacizumab or trastuzumab, and with letrozole in advanced breast cancer KU Leuven

Patrick Schöffski, Hans Wildiers
BACKGROUND: This phase Ib study (NCT00960960) evaluated pictilisib (GDC-0941; pan-phosphatidylinositol 3-kinase inhibitor) plus paclitaxel, with and without bevacizumab or trastuzumab, or in combination with letrozole, in patients with locally recurrent or metastatic breast cancer. METHODS: This was a three-part multischedule study. Patients in parts 1 and 2, which comprised 3 + 3 dose escalation and cohort expansion stages, received pictilisib ...

Cardiotoxicity associated with cancer therapy University of Antwerp

Rui Adao, Gilles De Keulenaer, Adelino Leite-Moreira, Carmen Bras-Silva
Cardiotoxicity is one of the most significant adverse effects of cancer treatment, and is responsible for considerable morbidity and mortality. Among the effects of chemotherapeutic agents on the cardiovascular system, the most frequent and serious is heart failure with ventricular systolic dysfunction. Other toxic effects include hypertension, thromboembolic disease, pericardial disease, arrhythmias and myocardial ischemia. For several decades, ...