The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer

Abstract

Lung cancer is the most common cancer and leading cause of cancer death. While targeted therapies have redefined treatment options for non-small cell lung carcinoma (NSCLC) with genetic aberrations such as epidermal growth factor and anaplastic lymphoma kinase, many patients do not harbour these oncogenic drivers. Cancer immunology has enabled the development of immune modulators that has dramatically altered the therapeutic landscape of advanced NSCLC. The success of immune-checkpoint inhibitors in pretreated NSCLC has led to the conduct of multiple studies exploring their role in the first-line setting. This article provides an overview of the evolving landscape of immune-checkpoint inhibitors with a focus on the programmed cell-death 1 (PD-1; pembrolizumab, nivolumab) and programmed cell-death ligand 1 (PD-L1; atezolizumab, durvalumab, avelumab) immune-checkpoint inhibitors as single agent or in combination with either chemotherapy or with another immune-checkpoint inhibitor in the treatment of NSCLC, the challenges faced, as well as future perspectives.

Keywords: anti-PD-1; anti-PD-L1; chemotherapy; combination immunotherapy; immunotherapy; non-small cell lung cancer (NSCLC).

Figure 1.

The evolving landscape of immune-checkpoint inhibitors in advanced non-small-cell lung cancer. FDA, US Food and Drug Administration; NSCLC, non-small-cell lung cancer; PD-L1, programmed cell-death ligand 1.

Figure 2.

Case of a 57-year-old man, never smoker, who presented with a retrocardiac mass on routine health screening. Subsequent investigations revealed a non-small-cell lung cancer, adenocarcinoma histologic subtype that was wildtype EGFR, and negative for ALK and ROS1 rearrangements. PD-L1 tumour proportion score using 22C3 immunohistochemistry was 30%. A CT PET was reported to show an FDG avid left lower-lobe pulmonary mass, pulmonary nodules, hepatic and bony lesions, and a large pericardial effusion. Carboplatin, pemetrexed and pembrolizumab were subsequently initiated. (a) Lung window of the CT PET at time of diagnosis and (b) CT thorax after four cycles of carboplatin/pemetrexed and pembrolizumab and 13 cycles of maintenance pemetrexed and pembrolizumab. CT, computed tomography; FDG, fluorodeoxyglucose; PD-L1, programmed cell-death ligand 1; PET, positron-emission tomography.

Figure 3.

Percentage of immune-related adverse events in selected phase III studies. (a) Percentage of immune-related adverse events (irAEs) in selected phase III studies of single-agent immune-checkpoint-inhibitor studies; (b) percentage of irAEs in selected phase III studies of immune-checkpoint inhibitor and chemotherapy combination studies

Figure 4.

Potential first-line treatment options for advanced non-small-cell lung cancer. For PD-L1 1–49%, we recommend pembrolizumab if the patient was unfit or declined chemotherapy. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; Mb, megabase; mut, mutations; PD-L1, programmed cell-death ligand 1; TMB, tumour mutation burden.