Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.

Charcot-Marie-Tooth hereditary neuropathy revealed after administration of docetaxel in advanced breast cancer.

Abstract: Charcot-Marie-Tooth (CMT) neuropathy is the most common hereditary cause of neuropathy. Diagnosis is usually not made during the childhood but in adolescence or late adulthood. It is reported in the literature that some neurotoxic chemotherapeutical agents can reveal an asymptomatic CMT IA hereditary neuropathy. To our knowledge, we report here the first case of CMT IA revealed in a 55-year-old woman after the administration of docetaxel/trastuzumab/pertuzumab for metastatic breast cancer. This case stresses again the necessity to obtain a complete personal and familial anamnesis and to perform a neurologic examination before the administration of neurotoxic chemotherapeutical agents to prevent the clinical expression of these hereditary neuropathies.

Recent advances and optimal management of human epidermal growth factor receptor-2-positive early-stage breast cancer.

Abstract: With the introduction of anthracycline-based regimens, 5-year survival rates have significantly improved in patients with early-stage breast cancer. With the addition of trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), improvements in overall survival have been observed among patients with advanced HER2-positive disease. Subsequently, lapatinib, an orally bioavailable small molecule dual HER2- and EGFR/HER1-specific tyrosine kinase inhibitor, received Food and Drug Administration (FDA) approval in combination with capecitabine for patients with advanced HER2+ breast cancer. Then, pertuzumab in 2012 and ado-trastuzumab emtansine in 2013 were approved in the US and elsewhere based on evidence showing an improvement in survival outcomes in patients with mostly trastuzumab naive or trastuzumab-exposed metastatic disease. The FDA also approved 1 year of extended adjuvant neratinib after chemotherapy and a year of trastuzumab for HER2-positive breast cancer on the basis of the ExteNET trial. The clinical benefit demonstrated by those drugs in advanced disease has triggered several adjuvant and neoadjuvant trials testing them in combination with chemotherapy, but also without conventional chemotherapy, using single or dual HER2-targeting drugs. In this article, we review the current data on the therapeutic management of HER2-positive early-stage breast cancer in the adjuvant and neoadjuvant setting. We also review the data the efficacy and safety of anthracycline-based and nonanthracycline-based adjuvant chemotherapy regimens combined with trastuzumab, and optimum chemotherapy regimens in small HER2-positive tumors.

Patient-reported function, health-related quality of life, and symptoms in APHINITY : pertuzumab plus trastuzumab and chemotherapy in HER2-positive early breast cancer

Abstract: Background We assessed health-related quality of life (symptoms of therapy/patient functioning/global health status), in APHINITY (pertuzumab/placebo, trastuzumab, and chemotherapy as adjuvant HER2-positive early breast cancer therapy). Methods Patients received 1 year/18 cycles of pertuzumab/placebo with trastuzumab and chemotherapy and completed EORTC QLQ-C30 and BR23 questionnaires until 36 months post-randomisation/disease recurrence. Changes ≥10 points from baseline were considered clinically meaningful. Results 87-97% of patients completed questionnaires. In the pertuzumab versus placebo arms, mean decrease in physical function scores (baseline → end of taxane) was -10.7 (95% CI -11.4, -10.0) versus -10.6 (-11.4, -9.9), mean decrease in global health status was -11.2 (-12.2, -10.2) versus -10.2 (-11.1, -9.2), and mean increase in diarrhoea scores (baseline → end of taxane) was +22.3 (21.0, 23.6) versus +9.2 (8.2, 10.2). Diarrhoea scores remained elevated versus baseline in the pertuzumab arm throughout HER2-targeted treatment (week 25: +13.2; end of treatment: +12.2). Role functioning was maintained in both arms. Conclusions Improved invasive disease-free survival achieved by adding pertuzumab to trastuzumab and chemotherapy did not adversely affect the ability to conduct activities of daily living versus trastuzumab and chemotherapy alone. Patient-reported diarrhoea worsened during taxane therapy in both arms, persisting during HER2-targeted treatment in the pertuzumab arm. CLINICALTRIALS.GOV: NCT01358877.

RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer.

Abstract: HER2 is a predictive biomarker for HER2-targeted therapeutics. For antibody–drug conjugates (ADCs; e.g., trastuzumab emtansine (T-DM1)), HER2 is utilized as a transport gate for cytotoxic agents into the cell. ADC biomarkers may therefore be more complex, also reflecting the intracellular drug transport. Here we report on a positive correlation between the early endosome marker RAB5A and T-DM1 sensitivity in five HER2-positive cell lines. Correlation between RAB5A expression and T-DM1 sensitivity is confirmed in breast cancer patients treated with trastuzumab emtansine/pertuzumab in the I-SPY2 trial (NCT01042379), but not in the trastuzumab/paclitaxel control arm. The clinical correlation is further verified in patients from the KAMILLA trial (NCT01702571). In conclusion, our results suggest RAB5A as a predictive biomarker for T-DM1 response and outline proteins involved in endocytic trafficking as predictive biomarkers for ADCs. Antibody Drug Conjugates (ADCs) are emerging in the field of precision cancer medicine. Here, the authors suggest using endocytosis as a predictive biomarker for response