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PD-1/PD-L1 Inhibitors for Non–Small Cell Lung Cancer: Incorporating Care Step Pathways for Effective Side-Effect Management

ABSTRACT: Programmed cell death protein 1 receptor and programmed cell death ligand 1 (PD-L1) inhibitors are immune checkpoint inhibitors (ICIs) that provide a survival benefit for select patients with advanced non–small cell lung cancer (NSCLC). Nivolumab, pembrolizumab, and atezolizumab are second-line therapies for advanced NSCLC after chemotherapy failure. Pembrolizumab and atezolizumab are also approved as first-line treatment for advanced NSCLC, and durvalumab is a PD-L1 inhibitor indicated as consolidation therapy in individuals with locally advanced NSCLC. The novel mechanism of action of these agents provides clear efficacy benefits to many NSCLC patients without good alternatives, but it may also result in unique immune-related adverse events that many health-care providers are unfamiliar with or uncertain about how to diagnosis and manage. Highlighting the resources of the Immuno-Oncology Essentials Initiative, particularly the Care Step Pathways (CSPs), this article addresses the role of the advanced practice provider in administration, side-effect identification and management, and education of patients with advanced NSCLC receiving ICI therapy. The diagnosis and management of pneumonitis, hypophysitis, diabetes mellitus, and arthralgias/myalgias are examined in detail, addressing special considerations in the NSCLC population.

SUBMITTER: Davies M

PROVIDER: S-EPMC7522661 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Project description:Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms "immunotherapy" and "chemotherapy". 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77-0.92), PFS (HR 0.80, 0.75-0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20-5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (≥ 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%-49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels.Systematic review registrationPROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678).

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PD-1/PD-L1 Inhibitors for Non–Small Cell Lung Cancer: Incorporating Care Step Pathways for Effective Side-Effect Management

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