Comparison of the toxicity profile of PD‐1 versus PD‐L1 inhibitors in non–small cell lung cancer: A systematic analysis of the literature

Pillai, Rathi N.; Behera, Madhusmita; Owonikoko, Taofeek K.; Kamphorst, Alice O.; Pakkala, Suchita; Belani, Chandra P.; Khuri, Fadlo R.; Ahmed, Rafi; Ramalingam, Suresh S.

doi:10.1002/cncr.31043

Cited by 270 publications

(253 citation statements)

References 37 publications

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“…1,2 In total, 6 IO agents targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (ipilimumab), programmed cell death 1 (PD-1) (nivolumab and pembrolizumab), or programmed cell death ligand 1 (PD-L1) (atezolizumab, avelumab, and durvalumab) gained US Food and Drug Administration approval as of January 2018. 1,2 In total, 6 IO agents targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (ipilimumab), programmed cell death 1 (PD-1) (nivolumab and pembrolizumab), or programmed cell death ligand 1 (PD-L1) (atezolizumab, avelumab, and durvalumab) gained US Food and Drug Administration approval as of January 2018.…”

Section: Introductionmentioning

confidence: 99%

The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced‐stage cancer treated with immunotherapy

Bilen

Martini

Liu

et al. 2018

Cancer

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126

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BACKGROUND: Optimal prognostic and predictive biomarkers for patients with advanced-stage cancer patients who received immunotherapy (IO) are lacking. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR), are readily available. The authors investigated the association between these markers and clinical outcomes of patients with advanced-stage cancer who received IO. METHODS: A retrospective review was conducted of 90 patients with advanced cancer who received treatment on phase 1 clinical trials of IO-based treatment regimens. NLR, MLR, and PLR values were log-transformed and treated as continuous variables for each patient. Overall survival (OS), progression-free survival (PFS), and clinical benefit were used to measure clinical outcomes. For univariate associations and multivariable analyses, Cox proportional-hazards models or logistic regression models were used. RESULTS: The median patient age was 63 years, and most were men (59%). The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). High baseline NLR, MLR, and PLR values were associated significantly with worse OS and PFS (P < .05) and a lower chance of benefit (NLR and PLR; P < .05). Increased NLR, MLR, and PLR values 6 weeks after baseline were associated with shorter OS and PFS (P ≤ .052). CONCLUSIONS: Baseline and early changes in NLR, MLR, and PLR values were strongly associated with clinical outcomes in patients who received IO-based treatment regimens on phase 1 trials. Confirmation in a homogenous patient population treated on late-stage trials or outside of trial settings is warranted. These values may warrant consideration for inclusion when risk stratifying patients enrolled onto phase 1 clinical trials of IO agents. Cancer 2019;125:127-134.

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Section: Introductionmentioning

confidence: 99%

The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced‐stage cancer treated with immunotherapy

Bilen

Martini

Liu

et al. 2018

Cancer

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126

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“…Systematic reviews comparing the toxicity profile of PD‐1 versus PD‐L1 inhibitors have shown that overall adverse events (AEs) and grade 3–5 AEs of PD‐1 and PD‐L1 inhibitors are similar . However, the efficacy of PD‐1 versus PD‐L1 inhibitors remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of PD‐1/PD‐L1 inhibitors in patients with advanced non‐small cell lung cancer: A meta‐analysis of randomized clinical trials

Peng

2019

Thoracic Cancer

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Background This meta‐analysis systematically evaluated the efficacy of PD‐1 and PD‐L1 inhibitors for the treatment of advanced non‐small cell lung cancer (NSCLC) and investigated the efficacy of first‐line therapy and PD‐1 versus PD‐L1 inhibitors. Methods PubMed, The Cochrane Library, and Embase were searched up to November 2018 for randomized controlled trials (RCTs) for eligible studies. The outcome of interest was overall survival (OS). The methodology was based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses and Cochrane Collaboration guidelines. Data were pooled by using the random effects model and expressed as hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Heterogeneity was assessed and quantified ( I 2 ). Results Seven RCTs were included in this study. PD‐1/PD‐L1 inhibitors achieved superior OS compared to chemotherapy (HR 0.72, 95% CI 0.63–0.82; P < 0.0001). OS was superior in previously treated patients compared to untreated patients (HR 0.69, 95% CI 0.63–0.76; HR 0.82, 95% CI 0.47–1.44, respectively). No significant differences in OS were observed between PD‐1 and PD‐L1 inhibitors (HR 0.71, 95% CI 0.59–0.86; HR 0.73, 95% CI 0.63–0.84, respectively). Conclusions PD‐1/PD‐L1 inhibitors significantly prolonged the OS of previously treated patients. No significant differences in OS were observed between PD‐1 and PD‐L1 inhibitors.

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“…Two studies have previously investigated the differences in the toxicities of PD1 and PD‐L1 inhibitors . Khunger et al reported a higher incidence of immune‐related pneumonitis with use of PD‐1 inhibitors compared with PD‐L1 inhibitors in patients with nonsmall cell lung cancer .…”

Section: Discussionmentioning

confidence: 99%

“…The summary of incidence of all‐grade and high‐grade pneumonitis was also reported in of our study. Pillai et al found a slight increase in pneumonitis risk with PD‐1 inhibitors . It should be noted that no RCT to date has directly compared the risk of immune‐related pneumonitis between PD‐1 and PD‐L1 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Risk of immune‐related pneumonitis for PD1/PD‐L1 inhibitors: Systematic review and network meta‐analysis

Huang

Fan

et al. 2019

Cancer Medicine

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Background Immune‐related pneumonitis is a clinically relevant and potentially life‐threatening adverse event. We performed a systematic review and network meta‐analysis to compare the risk of immune‐related pneumonitis among different PD 1/ PD ‐L1 inhibitor‐related therapeutic regimens. Methods Randomized controlled trials with PD 1/ PD ‐L1 inhibitors were identified through comprehensive searches of multiple databases. Both published and unpublished data were extracted. Bayesian NMA was performed using random‐effects models. All‐grade (Grade 1‐5) and high‐grade (Grade 3‐5) immune‐related pneumonitis were estimated using odds ratios ( OR s). Results A total of 25 studies involving 16 005 patients were included. Compared with chemotherapy, the OR s of immune‐related all‐grade and high‐grade pneumonitis were significant for nivolumab (all‐grade: OR = 6.29, 95% CrI: 2.67‐16.75; high‐grade: OR = 5.95, 95% CrI: 2.35‐17.29), pembrolizumab (all‐grade: OR = 5.78, 95% CrI: 2.79‐13.24; high‐grade: OR = 5.33, 95% CrI: 2.49‐12.97), and nivolumab plus ipilimumab therapy (all‐grade: OR = 14.82, 95% CrI: 5.48‐47.97; high‐grade: OR = 15.26, 95% CrI: 5.05‐55.52). Compared with nivolumab, nivolumab plus ipilimumab therapy was associated with an increased risk of all‐grade pneumonitis ( OR = 2.34, 95% CrI: 1.07‐5.77). Nivolumab plus ipilimumab therapy had the highest risk of both all‐grade and high‐grade pneumonitis among PD 1/ PD ‐L1 inhibitor‐related therapeutic regimens. Conclusions This study demonstrates that compared with chemotherapy, PD ‐1 inhibitor may result in a higher risk of immune‐related pneumonitis. Nivolumab plus ipilimumab therapy had the highest pneumonitis risk. These findings could be taken into account by the physicians in decision making.

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Comparison of the toxicity profile of PD‐1 versus PD‐L1 inhibitors in non–small cell lung cancer: A systematic analysis of the literature

Abstract: In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appear to be similar. Cancer 2018;124:271-7. © 2017 American Cancer Society.

Cited by 270 publications

References 37 publications

The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced‐stage cancer treated with immunotherapy

The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced‐stage cancer treated with immunotherapy

Efficacy of PD‐1/PD‐L1 inhibitors in patients with advanced non‐small cell lung cancer: A meta‐analysis of randomized clinical trials

Risk of immune‐related pneumonitis for PD1/PD‐L1 inhibitors: Systematic review and network meta‐analysis

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