Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study

Bjørnhart, Birgitte; Hansen, Karin Holmskov; Jørgensen, Trine Lembrecht; Herrstedt, Jørn; Schytte, Tine

doi:10.1080/0284186x.2019.1615636

Cited by 42 publications

(40 citation statements)

References 43 publications

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“…A number of recent studies has supported this hypothesis by showing favorable outcomes for patients with non-small cell lung cancer (NSCLC) and melanoma who developed various irAEs in response to immune checkpoint inhibition [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, a definite conclusion has not been drawn based on the findings from each single study, as contradictory results exist [23][24][25][26][27][28][29][30][31][32][33][34][35]. A systemic review included 16 studies and reported that irAEs such as pneumonitis, thyroid disorders, myalgias, and mucosal toxicity did not show a significant correlation with overall survival (OS) [36].…”

Section: Introductionmentioning

confidence: 99%

Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

Zhou

Yao

Yang

et al. 2020

BMC Med

241

162

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Background: A number of studies have reported an association between the occurrence of immune-related adverse events (irAEs) and clinical efficacy in patients undergoing treatment with immune checkpoint inhibitors (ICIs), but the results remain controversial. Methods: Under the guidance of a predefined protocol and Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, this meta-analysis included cohort studies investigating the association of irAEs and efficacy of ICIs in patients with cancer. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Subgroup analyses involving the cancer type, class of ICIs, combination therapy, sample size, model, landmark analysis, and approach used to extract the data were performed. Specific analyses of the type and grade of irAEs were also performed. Results: This meta-analysis included 30 studies including 4971 individuals. Patients with cancer who developed irAEs experienced both an OS benefit and a PFS benefit from ICI therapy compared to patients who did not develop irAEs (OS: hazard ratio (HR), 0.54, 95% confidence interval (CI), 0.45-0.65; p < 0.001; PFS: HR, 0.52, 95% CI, 0.44-0.61, p < 0.001). Subgroup analyses of the study quality characteristics and cancer types recapitulated these findings. Specific analyses of endocrine irAEs (OS: HR, 0.52, 95% CI, 0.44-0.62, p < 0.001), dermatological irAEs (OS: HR, 0.45, 95% CI, 0.35-0.59, p < 0.001), and low-grade irAEs (OS: HR, 0.57, 95% CI, 0.43-0.75; p < 0.001) yielded similar results. The association between irAE development and a favorable benefit on survival was significant in patients with cancer who were undergoing treatment with programmed cell death-1 inhibitors (OS: HR, 0.51, 95% CI, 0.42-0.62; p < 0.001), but not cytotoxic T-lymphocyte antigen-4 inhibitors (OS: HR, 0.89, 95% CI, 0.49-1.61; p = 0.706).

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Section: Introductionmentioning

confidence: 99%

Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

Zhou

Yao

Yang

et al. 2020

BMC Med

241

162

View full text Add to dashboard Cite

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“…Multimodality treatment of non-small cell lung cancer (NSCLC) has become more effective in recent years, e.g., due to stereotactic ablative radiotherapy for stage I disease [1,2] and oligometastatic stage IV disease [3][4][5], and immunotherapy for stage III and IV disease [6,7]. Patients with stage III disease who are unfit for radical chemoradiotherapy should be considered for reduced-intensity palliative chemoradiotherapy [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer

et al. 2020

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Introduction: Esophagitis influences quality of life and might cause treatment interruption and hospitalization. Previous studies of risk factors focused on curative treatment for non-small cell lung cancer (NSCLC), which often involves concomitant chemoradiation (CRT). Given the uncertainty around extrapolation of dose constraints, we analyzed risk factors in patients treated with hypofractionated palliative regimens. Patients and methods: A retrospective review of 106 patients treated with palliative radiotherapy or CRT between 2009 and 2017 was performed. Inclusion criteria: prescribed total dose 30-54 Gy, dose per fraction 2.5-4 Gy, esophageal dose > 1 Gy. Uni-and multivariate analyses were performed in 97 eligible patients to identify predictive factors for acute esophagitis grade ≥ 1 (CTCAE 5.0). Results: Forty percent of patients were treated with 15 fractions of 2.8 Gy (42 Gy) and 28% also received chemotherapy according to the CONRAD study regimen (induction and concomitant Carboplatin/Vinorelbine) published by the Norwegian Lung Cancer Group. Thirty-four percent were treated with 10 fractions of 3 Gy. Stage IV NSCLC was present in 47%. Esophagus Dmax was 39 Gy (population median) and Dmean 15 Gy. Overall 31% of patients developed esophagitis (26% grade 2-3, no grade 4-5). Several dosimetric parameters correlated with the risk of esophagitis (Dmax, Dmean, D5cc, V20, V30, V35, V40). Dmax outperformed other dosimetric variables in multivariate analysis. Furthermore, concomitant chemotherapy significantly increased the risk of esophagitis, while oral steroid medication reduced it. In patients with Dmax ≥40 Gy a reduced Dmean (≤20 Gy) was beneficial. Conclusion: In order to reduce esophagitis after hypofractionated palliative treatment lower doses than those recommended in curative NSCLC settings are preferable. Besides esophageal dose, CRT is the main risk factor for esophagitis. Additional work is needed to confirm that steroids are able to modify the risk (or to rule out confounding effects of baseline variables not included in our database).

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Section: Introductionmentioning

confidence: 99%

Risk factors for esophagitis after hypofractionated palliative (chemo)radiotherapy for non-small cell lung cancer

Nieder

Imingen²,

Mannsåker

et al. 2020

Preprint

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Introduction Esophagitis influences quality of life and might cause treatment interruption and hospitalization. Previous studies of risk factors mainly related to curative treatment for non-small cell lung cancer (NSCLC), which often involves concomitant chemoradiation (CRT). Given the uncertainty around extrapolation of dose constraints, we analyzed risk factors in patients treated with hypofractionated palliative regimens. Patients and Methods A retrospective review of 106 patients treated with palliative radiotherapy or CRT between 2009 and 2017 was performed. Inclusion criteria: prescribed total dose 30-54 Gy, dose per fraction 2.5-4 Gy, esophageal dose >1 Gy. Uni- and multivariate analyses were performed in 97 eligible patients to identify predictive factors for acute esophagitis grade ≥1 (CTCAE 5.0). Results Forty percent of patients were treated with 15 fractions of 2.8 Gy (42 Gy) and 28% also received chemotherapy according to the CONRAD study regimen (induction and concomitant Carboplatin/Vinorelbine) published by the Norwegian Lung Cancer Group. Thirty-four percent were treated with 10 fractions of 3 Gy. Stage IV NSCLC was present in 47%. Esophagus Dmax was 39 Gy (population median) and Dmean 15 Gy. Overall 31% of patients developed esophagitis (26% grade 2-3, no grade 4-5). Several dosimetric parameters correlated with the risk of esophagitis (Dmax, Dmean, D5cc, V20, V30, V35, V40). Dmax outperformed other dosimetric variables in multivariate analysis. Furthermore, concomitant chemotherapy significantly increased the risk of esophagitis, while oral steroid medication reduced it. In patients with Dmax ≥40 Gy a reduced Dmean (≤20 Gy) was beneficial. Conclusion In order to reduce esophagitis after hypofractionated palliative treatment lower doses than those recommended in curative NSCLC settings are preferable. Besides esophageal dose, CRT is the main risk factor for esophagitis. Additional work is needed to confirm that steroids are able to modify the risk (or to rule out confounding effects of baseline variables not included in our database).

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Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study

Cited by 42 publications

References 43 publications

Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis

Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer

Risk factors for esophagitis after hypofractionated palliative (chemo)radiotherapy for non-small cell lung cancer

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