First line Immunotherapy for Non-Small Cell Lung Cancer

Abstract

Immunotherapy for non-small cell lung cancer (NSCLC) is incorporated increasingly in first line treatments protocols. Multiple phase 3 studies have tested different medications targeting programmed death receptor 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), with or without chemotherapy. The inclusion criteria differ between the various clinical trials, including the cut-off levels of PD-L1 expression on tumor cells, and the tumor histology (squamous or non-squamous). Patients with tumor expression levels of PD-L1 ≥ 50% are candidates for treatment with single agent Pembrolizumab or Atezolizumab. Patients with PD-L1 < 50% are candidates for immunotherapy with pembrolizumab as a single agent if PL-1 > 1%; immunotherapy doublet, Nivolumab and Ipilimumab, or single agent immunotherapy combined with chemotherapy. Here we review phase 3 clinical trials utilizing immunotherapy in the first line for treatment of NSCLC, including Pembrolizumab in KEYNOTE-024, KEYNOTE-042, KEYNOTE-189 and KEYNOTE-407; Nivolumab and Ipilimumab in CHECKMATE-227 and CHECKMATE 9LA; and Atezolizumab in IMpower110, IMpower130 and IMpower150.

Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics

“…Recurrence-free survival was higher in patients with a higher PD-L1 expression, though all patients experienced greater benefit when treated with nivolumab compared to ipilimumab (51). In May 2020, treatment with nivolumab in combination with ipilimumab was approved for first-line treatment of patients with metastatic or recurrent NSCLC with no EGFR or ALK genomic tumor aberrations (65). Patients were enrolled in the CheckMate 9LA trial regardless of PD-L1 status, and randomized to receive nivolumab with ipilimumab and chemotherapy or chemotherapy alone, with cohorts stratified based on PD-L1 status (< 1% vs ≥ 1%) (57).…”

Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe?

“…To this end, immunotherapies based on, e.g., administration of genetically engineered cancer specific effector cells (so-called CAR T cells [ 21 ]) or monoclonal antibodies (mAb) [ 22 ] that breach checkpoint inhibitory (CPI) molecules on immune cells, have revolutionized the treatment of disseminated cancers over the past decade. CPI has now been approved for treatment in numerous cancers, e.g., melanoma, head and neck cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and bladder cancer, and in some diseases these immunotherapeutic drugs are now first-line treatments [ 23 ]. The fundamental mechanism of CPI therapy is unleashing the inhibition of spontaneously induced T and natural killer (NK) cell responses, allowing more efficient anti-tumor immune responses.…”

Scutellaria baicalensis and Their Natural Flavone Compounds as Potential Medicinal Drugs for the Treatment of Nicotine-Induced Non-Small-Cell Lung Cancer and Asthma

“…NSCLC is still the leading cause of death, despite the prominent progress in the prognosis over the last years [ 1 ]. Monoclonal antibodies such as atezolizumab, nivolumab, pembrolizumab and bevacizumab targeting inhibitory immune checkpoint molecules have shown novel immunotherapies agent in locally advanced NSCLC [ 11 , 19 ]. Treatment with chemotherapeutic agents (e.g., cisplatin) in combination with monoclonal antibodies may provide benefits in patients with metastasized stage NSCLC [ 19 , 20 ].…”

“…Monoclonal antibodies such as atezolizumab, nivolumab, pembrolizumab and bevacizumab targeting inhibitory immune checkpoint molecules have shown novel immunotherapies agent in locally advanced NSCLC [ 11 , 19 ]. Treatment with chemotherapeutic agents (e.g., cisplatin) in combination with monoclonal antibodies may provide benefits in patients with metastasized stage NSCLC [ 19 , 20 ]. Therapeutic agents such as afatinib, osimertinib, gefitinib and erlotinib have shown promising results in patients with NSCLC who have driver mutations such as epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) [ 19 ].…”