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

Abstract

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.

Sub-cutaneous Fat Mass measured on multislice computed tomography of pretreatment PET/CT is a prognostic factor of stage IV non-small cell lung cancer treated by nivolumab

“…Cancers have the ability to disrupt immune response by interfering with adaptive immunity. 3,4 Immunotherapy using immune checkpoint inhibitors, notably anti-PD-1 (programmed cell death protein-1) and anti-PDL-1 (PD1 ligand) antibody, has been shown to improve outcome of stage IIIb/IV NSCLC and is a new standard of care. 5,6 In this setting, pembrolizumab, nivolumab, and atezolizumab have been approved by the Food and Drug Administration FDA and the European Medicines Agency as first-(pembrolizumab) and second-line treatment.…”

EBUS-TNBA 22G samples: Comparison of PD-L1 expression between DAKO and BIOCARE®

“…The investigation of PD-L1 expression in patients with advanced stage disease is crucial. Previously published studies in NSCLC with immunotherapy as first line treatment alone have presented increased progression free survial and longlasting responses in specific patients with increased PD-L1 expression [21,22]. Currently there is an investigation towards combining chemotherapy and/or radiotherapy in order to increase the immunotherapy treating effect as first line treatment [23,24].…”

Recent advances in targeted small‐molecule inhibitor therapy for non–small‐cell lung cancer—An update

“…It is a humanized immunoglobulin (Ig) G4 kappa PD‐1 monoclonal antibody, approved by the US FDA in 2015, European Medicines Agency (EMA), and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) as first‐line therapy for patients with chemotherapy naïve metastatic NSCLC and high PD‐L1 expression [tumour proportion score (TPS) 50%] with no EGFR or ALK genomic mutations …”