title: Incorporating immune-checkpoint inhibitors into systemic therapy of NSCLC.
abstract: Despite current therapeutic options metastatic non- small-cell lung cancer (NSCLC) remains incurable. Targeted therapies have opened new opportunities for several molecular subtypes, but virtually all patients treated will ultimately develop progressive disease by treatment resistance. Recent clinical trials have shown that immune-checkpoint blockade can result in striking and durable responses in metastatic NSCLC. These impressive results are yet to be confirmed in following trials; nonetheless, NSCLC therapeutic strategies will most likely need to integrate immune-checkpoint inhibitors in the near future. Interestingly, conventional therapies are capable of modulating the immune system and can therefore interact directly or indirectly with immunotherapies. This suggests that some combinations might have synergistic activity and lead to improved efficacy. Conventional and targeted therapies can induce rapid tumor lysis, and immune-checkpoint blockade can then help to induce a sustained immune-mediated tumor control. Moreover, the distinctive toxicity profile associated with immune-checkpoint modulators makes them good candidates for combination strategies. Here we summarize the results of immune-checkpoints trials in NSCLC, and also report how current therapeutic options can modulate the immune system. We provide a rationale and identify potential challenges for immune-checkpoint blockade combinations with conventional therapeutics in NSCLC.
authors.affiliation: *SITEP (Service d'Innovations Therapeutiques Precoces), Department of Medicine, Gustave Roussy, †Institut Gustave Roussy, University Paris Sud, Villejuif, France; ‡Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; §Thoracic Multidisciplinary Committee, Gustave Roussy, University Paris Sud, Villejuif, France; and ‖Department of Medical Oncology, University of Athens School of Medicine, Athens, Greece.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Champiat
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Ileana
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Giannis
authors.initials: G
authors.lastname: Mountzios
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor