title: One step forward, two steps back: The story of everolimus in advanced breast cancer.
abstract: There has been a substantial surge of 'targeted agents' in contemporary anticancer drug armamentarium and some of these agents have revolutionized the outcome of cancer patients. However, on contrary to the nomenclature, not all new targeted agents are selected based on presence of target molecules on the cancer cells. Drugs are typically approved based on demonstration of benefit in randomized controlled trials with regards to efficacy outcomes although both the 'benefits' and 'outcomes' are defined inconsistently. Surrogates that are not validated properly are often used as endpoints. Furthermore, new anticancer drugs are frequently associated with increased inconvenience to the patients and/or to the society due to added toxicity and cost. In this perspective article, emphasis is given to the above problems focusing on room for improvement in anticancer drug development. An illustration of a recently approved drug to treat advanced breast cancer, everolimus and a previously revoked drug bevacizumab is given.
authors.affiliation: Department of Medical Oncology and Hematology, CancerCare Manitoba and University of Manitoba, Winnipeg, MB, R3E 0V9, Canada. Electronic address: sniraula@Cancercare.mb.ca.
authors.forename: Saroj
authors.initials: S
authors.lastname: Niraula
authors.affiliation: Medical Oncology Department, Albacete University Hospital and AECC Unit, Albacete, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocana
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Center and University of Toronto, Toronto, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D023381:Endpoint Determination; D000068338:Everolimus / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D000068338:Everolimus
keywords: Biomarkers; Breast cancer; Everolimus; Randomized controlled trial; mTOR