Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials

Luo, Wenxin; Wang, Zhoufeng; Tian, Panwen; Li, Weimin

doi:10.1007/s00432-018-2707-4

Cited by 58 publications

(42 citation statements)

References 23 publications

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“…Progressive generalized muscle weakness and respiratory or cardiac muscle involvement represent the most prominent life‐threatening consequences of irMyositis but are detected only in a small proportion of patients. Ten percent to 20% of patients ultimately require non‐invasive or mechanical ventilation . Concurrent myocarditis is diagnosed in 25% to 35% of patients, being more frequent and severe in patients receiving ICIs combination .…”

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

“…A meta‐analysis reported that the overall incidence of sensory peripheral neuropathy was in 1.2% in patients on PD‐1/PD‐L1 inhibitors vs 8.6% in patients receiving chemotherapy agents (risk ratio (RR): 0.16; 95% CI: 0.10‐0.26; P < .001), of which 0.3% vs 1.1% (RR: 0.20; 95% CI: 0.05‐0.77; P = .0019) were severe . Another meta‐analysis on patients with non‐small cell lung cancer (NSCLC) documented all‐grade sensory peripheral neuropathy in 1.32% of those under PD‐1/PD‐L1 therapy vs 6.31% in those under chemotherapy agents (RR: 0.13; 95% CI: 0.05‐0.34; P < .0001); none of the patients in the PD‐1/PD‐L1 group had high‐grade peripheral sensory neuropathy vs 0.61% of patients under chemotherapy (RR: 0.10; 95% CI: 0.02‐0.53; P = .0068), suggesting that, overall, anti‐PD‐1/PD‐L1 inhibitors are safer and better tolerated than cytotoxic chemotherapy . With concurrent use of ICIs and neurotoxic chemotherapy, data to date do not show increased rates of grade 3 or 4 peripheral neuropathy (8.2% with nab‐paclitaxel with or without ICIs) …”

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

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Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

Psimaras

Velasco

Birzu

et al. 2019

J Peripheral Nervous Sys

122

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Immune checkpoint inhibitors (ICIs) are increasingly used and are becoming the standard of care in the treatment of various tumor types. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events (irAEs). Neurological irAEs are rare but potentially severe. Neuromuscular disorders represent the most common neurological irAEs following anti-PD-1, anti-PD-L1, and anti-CTLA-4 treatment, and include myositis, myasthenia gravis, and demyelinating polyradiculoneuropathy. Instrumental findings may differ from typical neuromuscular disorders occurring outside ICIs treatment.Despite initial severity, neurological irAEs often respond to immune-modulating therapies. Prompt irAEs diagnosis, ICIs discontinuation, and early treatment with corticosteroids, together with patient education and a multi-disciplinary approach, are important for optimizing clinical outcomes. Intravenous immunoglobulin, plasma exchange, and other immune-modulating treatments should be considered in more severe cases. Consideration of re-challenging with the same immunotherapy drug may be given in some cases, based on clinical picture and initial severity of irAEs. K E Y W O R D SCTLA-4, demyelinating polyradiculoneuropathy, immune checkpoint inhibitor, myasthenia gravis, myositis, nivolumab, PD-1, PD-L1, pembrolizumab, peripheral neuropathy

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Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

Section: Clinical Syndromes and Presentationsmentioning

confidence: 99%

Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

Psimaras

Velasco

Birzu

et al. 2019

J Peripheral Nervous Sys

122

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“…The previous meta-analysis focused on the safety of PD-1/PD-L1 inhibitors in lung cancer and showed that the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appeared to be similar. 47 – 49 …”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis

Peng¹,

Li²,

Gu³

et al. 2018

OTT

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The value of immune checkpoint inhibitor (ICI) combination therapy for patients with lung cancer remains unclear. We conducted a meta-analysis using PubMed, Embase, and ClinicalTrials.gov databases to identify eligible randomized controlled trials (RCTs) that might provide a reference for clinical practice. The selection criteria were defined according to the population, intervention, comparison, outcome and study design (PICOS) framework. In all, 12 RCTs with 5,989 patients were included in this meta-analysis. Our results showed that ICI combination therapy was significantly associated with the improvement of overall response rate (ORR) (RR =1.44 [95% CI 1.19, 1.74], P=0.0002), progression-free survival (PFS) (HR =0.67 [95% CI 0.59, 0.77], P<0.00001), and OS (HR =0.81 [95% CI 0.70, 0.95], P=0.008) in lung cancer. In subgroup analyses, combination ICI therapy significantly prolonged OS in non-small-cell lung cancer (NSCLC) patients (HR =0.80 [95% CI 0.73, 0.88], P<0.00001) but not in SCLC (HR =0.94 [95% CI 0.82, 1.08], P=0.40) patients. Data suggested that PD-1 inhibitors had higher efficacy and safety profiles than PD-L1 and CTLA-4 inhibitors in combination ICI therapy for lung cancer patients. Furthermore, tolerability analysis revealed higher incidences of grade ≥3 AEs, fatigue, and increased transaminases from combination ICI therapy. In conclusion, our meta-analysis indicated that combination ICI therapy should be considered in clinical practice and future study designs for NSCLC patients. However, the current data do not support the large-scale clinical application of combination ICI therapy in SCLC patients.

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“…In advanced NSCLC, immune-related colitis is the third most frequent high-grade immune-related adverse event with the use of programmed death 1/programmed death ligand 1 inhibitors, affecting 0.4% of patients. 1 In extreme cases, immune-related colitis can lead to bowel perforation, although only one other case report describes this in a patient treated with nivolumab for NSCLC.…”

Section: To the Editormentioning

confidence: 99%

Nivolumab-Induced Fulminant Immune-Related Colitis Despite Infliximab in a Patient With NSCLC

Callens

Tamsin

Zandweghe

2019

Journal of Thoracic Oncology

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Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials

Cited by 58 publications

References 23 publications

Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

Immune checkpoint inhibitors‐induced neuromuscular toxicity: From pathogenesis to treatment

The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis

Nivolumab-Induced Fulminant Immune-Related Colitis Despite Infliximab in a Patient With NSCLC

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