Which medications in the drug class PD-1/PD-L1 Inhibitors are used in the treatment of Non-Small Cell Lung Cancer (NSCLC)?

Updated: Jul 15, 2021
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Answer

PD-1/PD-L1 Inhibitors

PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells. Under normal conditions, PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound. This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation. Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PD-L1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells; therefore, inhibiting the ligand binding will enhance T-cell mediated immune response.

Nivolumab (Opdivo)

Monoclonal antibody to programmed cell death-1 protein (PD-1). It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Restores cytokine secretion and T cell activity. It is indicated for metastatic squamous and nonsquamous (including adenocarcinoma) NSCLC with progression on or after platinum-based chemotherapy. It is also indicated in combination with ipilimumab, for metastatic NSCLC in patients whose tumors express PD-L1 (≥1%), with no EGFR or ALK tumor aberrations.

Pembrolizumab (Keytruda)

Pembrolizumab is a monoclonal antibody to programmed cell death-1 protein (PD-1). It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. It is indicated as a single agent for first-line treatment of patients with stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC whose tumors express PD-L1 (Tumor Proportion Score [TPS] ≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. Pembrolizumab is also indicated as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.

Pembrolizumab is indicated in combination with pemetrexed and carboplatin for first-line treatment of patients with metastatic nonsquamous NSCLC irrespective of PD-L1 expression. It is also indicated first-line in combination with carboplatin and either paclitaxel or nab-paclitaxel for patients with metastatic squamous NSCLC.

Atezolizumab (Tecentriq)

Atezolizumab is a monoclonal antibody to PD-L1. It is indicated for patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab. It is also indicated for first-line treatment for metastatic NSCLC in patients whose tumors have high PD-L1 expression (PD-L1 stained ≥50% of tumor cells [TC ≥50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥10% of the tumor area [IC ≥10%]).

Durvalumab (Imfinzi)

Human IgG1 kappa monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, and therefore overcoming/preventing PD-L1-mediated inhibition/suppression of T-cell activation. It is indicated for unresectable, Stage III NSCLC in patients whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

Cemiplimab (Libtayo, Cemiplimab-rwlc)

Cemiplimab is a recombinant human IgG4 monoclonal antibody that binds to PD-1 and blocks its interaction with PD-L1 and PD-L1, releasing the PD-1 pathway-mediated inhibition of the immune response, including antitumor immune response, thereby decreasing tumor growth. Binding of the PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. It is approved for first-line treatment of NSCLC who tumors have high PD-L1 expression [TPS ≥50%] with no EGFR, ROS-1, or ALK mutations.

Ipilimumab (Yervoy)

Recombinant, human cytotoxic T-lymphocyte antigen. Proposed mechanism of action is indirect, possibly through inhibition of CTLA-4 signaling, which can in turn reduce T-regulatory cell function and may contribute to a general increase in T cell responsiveness, including the anti-tumor immune response. It is indicated in combination with nivolumab, for metastatic NSCLC in patients whose tumors express PD-L1 (≥1%), with no EGFR or ALK tumor aberrations.


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