Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 85% of all cases. Until recently, chemotherapy – characterized by some benefit but only rare durable responses – was the only treatment option for patients with NSCLC whose tumors lacked targetable mutations. By contrast, immune checkpoint inhibitors have demonstrated distinctly durable responses and represent the advent of a new treatment approach for patients with NSCLC. Three immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab, are now approved for use in first- and/or second-line settings for selected patients with advanced NSCLC, with promising benefit also seen in patients with stage III NSCLC. Additionally, durvalumab following chemoradiation has been approved for use in patients with locally advanced disease. Due to the distinct features of cancer immunotherapy, and rapid progress in the field, clinical guidance is needed on the use of these agents, including appropriate patient selection, sequencing of therapies, response monitoring, adverse event management, and biomarker testing. The Society for Immunotherapy of Cancer (SITC) convened an expert Task Force charged with developing consensus recommendations on these key issues. Following a systematic process as outlined by the National Academy of Medicine, a literature search and panel voting were used to rate the strength of evidence for each recommendation. This consensus statement provides evidence-based recommendations to help clinicians integrate immune checkpoint inhibitors into the treatment plan for patients with NSCLC. This guidance will be updated following relevant advances in the field.
Highlights
Lung cancer is associated with profound medical, psychosocial, economic, and societal burden
Results from the CheckMate 227 phase III clinical trial indicate that patients with advanced non-small cell lung cancer (NSCLC) – squamous and non-squamous – and high tumor mutational burden (TMB, measured with the FoundationOne CDxTM assay) had increased progression-free survival (PFS) when treated with first-line combination nivolumab + ipilimumab compared to chemotherapy, regardless of tumor programmed death- ligand 1 (PD-L1) expression (HR 0.58; 97.5%CI: 0.41–0.81; p < 0.001)
Presented data from this study indicate that patients with advanced NSCLC treated with nivolumab + chemotherapy had increased median PFS compared to patients treated with chemotherapy alone (5.6 mos vs 4.7 mos, respectively; HR = 0.74 [95% CI: 0.58–0.94]) [32]
Summary
Lung cancer is associated with profound medical, psychosocial, economic, and societal burden. Four immune checkpoint pathway inhibitors have been approved by the United Stated Food and Drug Administration (FDA) for use in patients with NSCLC: nivolumab and pembrolizumab, both targeting the programmed cell death-1 (PD-1) receptor, as well as atezolizumab and durvalumab, targeting the anti-programmed death- ligand 1 (PD-L1) [9, 17]. Alongside these approvals, companion and complementary diagnostic assays measuring PD-L1 as a predictive biomarker in the tumor microenvironment have been approved to aid in patient selection [18]. Variability in assay systems, tissue preparation and processing, and cutoff values have complicated the interpretation and consensus use of these assays [18,19,20]
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