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Drug‐conjugated antibodies for the treatment of cancer
Author(s) -
Lambert John M.
Publication year - 2013
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12044
Subject(s) - medicine , brentuximab vedotin , lapatinib , trastuzumab emtansine , trastuzumab , oncology , clinical trial , cancer , capecitabine , drug , breast cancer , metastatic breast cancer , phases of clinical research , lymphoma , pharmacology , hodgkin lymphoma , colorectal cancer
Despite considerable effort, application of monoclonal antibody technology has had only modest success in improving treatment outcomes in patients with solid tumours. Enhancing the cancer cell‐killing activity of antibodies through conjugation to highly potent cytotoxic ‘payloads’ to create antibody–drug conjuates ( ADCs ) offers a strategy for developing anti‐cancer drugs of great promise. Early ADCs exhibited side‐effect profiles similar to those of ‘classical’ chemotherapeutic agents and their performance in clinical trials in cancer patients was generally poor. However, the recent clinical development of ADCs that have highly potent tubulin‐acting agents as their payloads have profoundly changed the outlook for ADC technology. Twenty‐five such ADCs are in clinical development and one, brentuximab vedotin, was approved by the FDA in A ugust, 2011, for the treatment of patients with Hodgkin's lymphoma and patients with anaplastic large cell lymphoma, based on a high rate of durable responses in single arm phase II clinical trials. More recently, a second ADC , trastuzumab emtansine, has shown excellent anti‐tumour activity with the presentation of results of a 991‐patient randomized phase III trial in patients with HER2 ‐positive metastatic breast cancer. Treatment with this ADC (single agent) resulted in a significantly improved progression‐free survival of 9.6 months compared with 6.4 months for lapatinib plus capecitabine in the comparator arm and significantly prolonged overall survival. Besides demonstrating excellent efficacy, these ADCs were remarkably well tolerated. Thus these, and other ADCs in development, promise to achieve the long sought goal of ADC technology, that is, of having compounds with high anti‐tumour activity at doses where adverse effects are generally mild.