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.

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A dose of 200 mg 3‐weekly of pembrolizumab was approved by the Food and Drug Administration (FDA) as treatment for advanced non‐small cell lung cancer (NSCLC) without oncogenic drivers. This is despite evidence showing no difference in efficacy with 2 mg/kg. Our study aimed to assess the efficacy of a lower fixed dose of 100 mg, which is closer to 2 mg/kg weight‐based dose in an average‐sized Asian patient. All patients receiving pembrolizumab for advanced NSCLC from January 2016 to March 2020 in National University Hospital, Singapore, were included in this retrospective observational study. The effect of pembrolizumab 100 mg (Pem100) vs 200 mg (Pem200) upon survival outcomes, toxicity and cost were examined. One hundred fourteen patients received pembrolizumab. Sixty‐five (57%) and 49 (43%) received Pem100 and Pem200, respectively. There was no difference in progression‐free survival (PFS) and overall survival (OS) between Pem100 vs Pem200 as a single agent (PFS: 6.8 vs 4.2 months, hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.36‐1.46, P = .36; 9 month OS: 58% vs 63%, HR 1.08, 95% CI 0.48‐2.41, P = .86) and when combined with chemotherapy (9‐month PFS: 60% vs 50%, HR0.84, 95% CI 0.34‐2.08, P = .71; 9‐month OS: 85% vs 58%, HR 0.27, 95% CI 0.062‐1.20, P = .09). No significant difference in response rate or ≥G3 immune‐related toxicities between Pem100 and Pem200 was observed. A cost minimisation analysis evaluating the degree of cost savings related to drug costs estimated a within study cost saving of SGD4,290,912 and cost saving per patient of SGD39,942 in the Pem100 group. A 100 mg of pembrolizumab appears to be effective with reduction in cost. A randomised trial should be done to investigate a lower dose of pembrolizumab.

<b><i>Background:</i></b> The approved doses of the single agent nivolumab – an anti-programmed cell death protein 1 (PD-1) monoclonal antibody – for renal cell carcinoma (RCC) are 3 mg/kg and a 240-mg flat dose, despite efficacy shown at lower doses in earlier CheckMate trials. In view of financial constraints, the minimum dose of nivolumab required for efficacy remains a critical area of inquiry. <b><i>Methods:</i></b> A retrospective review of RCC patients receiving single-agent anti-PD-1 treatment was conducted. Using the median cutoff of the maximum dose per body weight received, we investigated the effect of lower dosages on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse event-free survival (irAE-FS). Survival analysis was made by Kaplan-Meier, by uni- and multivariable Cox models, and by modeling the statistical interaction between dosages and survival. <b><i>Results:</i></b> 32 patients were recruited: 8 patients (25%) receiving first-line treatment and 24 (75%) receiving second-line treatment and beyond. A median split at 2.15 mg/kg yielded 16 patients in both the lower-dose (LD) and the higher-dose (HD) cohort. Hazard ratios (HRs) demonstrated no difference in OS after adjustment for gender (HR = 0.22, 95% CI 0.05–1.05, <i>p</i> = 0.054; favoring LD), as well as in PFS after adjustment for gender and concurrent radiation therapy (HR = 0.58, 95% CI 0.25–1.34, <i>p</i> = 0.210; favoring LD). No differences in ORR were observed (50.0 vs. 43.8%, <i>p</i> = 1.00, in the LD and the HD cohort, respectively). Immune-related phenomena were observed in the LD group, including pseudoprogression and increased all-grade immune-related toxicities (irAE-FS: HR = 1.72, 95% CI 0.48–6.14, <i>p</i> = 0.293; favoring HD). Iterative dichotomization of dosages showed no dose-OS or dose-irAE-FS relationship. <b><i>Conclusion:</i></b> Our study suggests no apparent reduction in efficacy when using a low-dosage nivolumab regimen.