Novel Formulations and New Mechanisms of Delivering Chemotherapy

Abstract

The identification of epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements and the development of targeted therapy for patients with these molecular alterations has been a tremendous advance in the treatment of advanced stage or metastatic non-small cell lung cancer (NSCLC). However, the majority of patients with advanced stage NSCLC will not have one of these molecular alterations and will receive chemotherapy as their primary therapy. Chemotherapy remains a critical component of therapy for resected and locally advanced NSCLC, as well as for patients with limited-stage and extensive stage small cell lung cancer (SCLC). A significant unmet need exists to develop novel chemotherapy agents and to improve the efficacy and toxicity of currently available agents. Several novel formulations of currently available chemotherapy agents are in development for NSCLC and SCLC. Antibody conjugates are therapeutic agents that employ a tumor-specific monoclonal antibody conjugated to a cytotoxic or radionuclide agent. After the monoclonal antibody binds to the tumor antigen, these agents are internalized, and the link between the antibody and the therapeutic agent is dissolved and the cytotoxic agent is release intracellularly. This enhanced delivery of chemotherapy to malignant tissues has the potential to improve efficacy and reduce toxicity. Antibody conjugates to therapeutic agents are currently available for other malignancies and are in development for NSCLC and SCLC.KEY POINTSThe majority of patients with advanced-stage non-small cell lung cancer (NSCLC) and all patients with extensive stage small cell lung cancer (SCLC) receive chemotherapy as their primary therapy.Novel formulations of current chemotherapy agents have the potential to reduce toxicity and improve efficacy over previous formulations.Antibody-drug conjugates use an antibody against a tumor-specific antigen that is linked to a therapeutic agent to improve delivery to malignant cells and reduce exposure of normal cells.Antibody conjugates are currently approved for use for non-Hodgkin lymphoma, Hodgkin lymphoma, and HER2-positive breast cancer.Ongoing trials are evaluating the safety and efficacy of several novel formulations of chemotherapy and antibody-drug conjugates or drug conjugates in NSCLC and SCLC.