First line Immunotherapy for Non-Small Cell Lung Cancer

Area of Science:

• Oncology
• Immunology
• Clinical Trials

Background:

• Immunotherapy, targeting programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), is increasingly used in first-line non-small cell lung cancer (NSCLC) treatment.
• Various phase 3 studies have evaluated different immunotherapy agents, alone or with chemotherapy, with differing inclusion criteria regarding PD-L1 expression and tumor histology.

Purpose of the Study:

• To review phase 3 clinical trials of first-line immunotherapy for non-small cell lung cancer.
• To summarize the efficacy of different immunotherapy regimens based on PD-L1 expression and histology.

Main Methods:

• Review of phase 3 clinical trials including Pembrolizumab (KEYNOTE-024, -042, -189, -407), Nivolumab and Ipilimumab (CHECKMATE-227, -9LA), and Atezolizumab (IMpower110, -130, -150).
• Analysis of treatment eligibility based on programmed death-ligand 1 (PD-L1) expression cut-offs (≥50% or <50%) and tumor histology (squamous or non-squamous).

Main Results:

• Patients with PD-L1 ≥ 50% expression are candidates for single-agent Pembrolizumab or Atezolizumab.
• Patients with PD-L1 < 50% expression may receive single-agent Pembrolizumab (if PD-L1 > 1%), Nivolumab/Ipilimumab combination, or immunotherapy plus chemotherapy.

Conclusions:

• First-line immunotherapy offers diverse treatment strategies for NSCLC.
• Treatment selection depends on PD-L1 expression levels and tumor histology, guiding the choice between single-agent immunotherapy, combination immunotherapy, or chemo-immunotherapy.