PD-1 blockade in advanced NSCLC: A focus on pembrolizumab

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers and is responsible for a large proportion of all cancer-related deaths. Current treatment options are inadequate, reflecting a substantial unmet clinical need. Increasing knowledge regarding the mechanisms and genetic aberrations underlying tumor development and growth has heralded a new era of therapy in oncology, moving away from indiscriminate cytotoxic chemotherapy toward more finely focused, targeted medicine. The development of small-molecule drugs and monoclonal antibodies directed toward specific components of dysfunctional molecular or immune pathways, and mutated genes specific to particular cancer types, is leading the field to more personalized and less toxic treatment options, many of which have demonstrated greater efficacy and survival benefits than their chemotherapeutic counterparts. Particularly successful examples are agents that interfere with the programmed death 1 (PD-1) pathway, which many tumors can hijack to avoid immune surveillance and editing. Pembrolizumab, a monoclonal antibody directed at PD-1 that blocks the engagement between PD-1 and its ligands, has been explored as a treatment for solid tumors, and demonstrated survival benefits in several studies. The use of PD-1 inhibitors such as nivolumab and pembrolizumab in advanced cancers is widespread, and pembrolizumab is available in more than 60 countries for at least one of the following: advanced melanoma, PD-L1-expressing NSCLC, head and neck squamous cell carcinoma, and adult and pediatric patients with refractory classical Hodgkin's lymphoma. This work provides a brief overview of the role of pembrolizumab in the treatment of advanced (recurrent/metastatic) NSCLC.