Impact of previous corticosteroid exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective observational study

Background Immunosuppressive dosing of corticosteroids at the start of treatment impairs immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC). Previous cumulative dose and intake modality of corticosteroids may result in different levels of immunosuppression. We...

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Veröffentlicht in:Cancer chemotherapy and pharmacology 2022-04, Vol.89 (4), p.529-537
Hauptverfasser: Nelli, F., Virtuoso, A., Berrios, J. R. Giron, Giannarelli, D., Fabbri, A., Marrucci, E., Ruggeri, E. M.
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container_end_page 537
container_issue 4
container_start_page 529
container_title Cancer chemotherapy and pharmacology
container_volume 89
creator Nelli, F.
Virtuoso, A.
Berrios, J. R. Giron
Giannarelli, D.
Fabbri, A.
Marrucci, E.
Ruggeri, E. M.
description Background Immunosuppressive dosing of corticosteroids at the start of treatment impairs immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC). Previous cumulative dose and intake modality of corticosteroids may result in different levels of immunosuppression. We sought to determine whether these aspects could predict disease control and survival in NSCLC patients receiving ICIs. Methods We conducted a retrospective single-center study, including patients treated with ICI as second-line therapy at our institution between July 2015 and February 2021. A prednisone equivalent threshold of 700 mg defined low (LCD) or high (HCD) cumulative dosing during the 90 days before starting ICIs. At least one 5-day course of ≥ 10 mg prednisone equivalent determined whether the intake was pulse (PCD, ≤ 5 days) or continuous (CCD, > 5 days). Results We included 113 consecutive patients. Durable control benefit and no clinical benefit (NCB) were reported in 53 (47%) and 60 (53%) of the cases, respectively. ECOG PS 1–2, negative PD-L1 expression, HCD, and CCD were significantly related to NCB in multivariate analysis. The median PFS was 4.6 months (95%CI: 3.9–6.3) and median OS was 6.9 months (95% CI: 6.0–8.9) after a median follow-up time of 43.5 months (95% CI: 32.6–54.4). Multivariate analysis of survival confirmed ECOG PS 1–2 ( p  = 0.005), negative PD-L1 expression ( p  = 0.002), and CCD ( p  = 0.001) significantly correlated with an increased risk of mortality. Conclusions These findings imply that immunosuppressive corticosteroid dosing before ICIs, even of short duration, might affect survival. The constraints of this study and lack of reliable comparisons suggest a hypothesis-generating value of these results.
doi_str_mv 10.1007/s00280-022-04416-4
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R. Giron ; Giannarelli, D. ; Fabbri, A. ; Marrucci, E. ; Ruggeri, E. M.</creator><creatorcontrib>Nelli, F. ; Virtuoso, A. ; Berrios, J. R. Giron ; Giannarelli, D. ; Fabbri, A. ; Marrucci, E. ; Ruggeri, E. M.</creatorcontrib><description>Background Immunosuppressive dosing of corticosteroids at the start of treatment impairs immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC). Previous cumulative dose and intake modality of corticosteroids may result in different levels of immunosuppression. We sought to determine whether these aspects could predict disease control and survival in NSCLC patients receiving ICIs. Methods We conducted a retrospective single-center study, including patients treated with ICI as second-line therapy at our institution between July 2015 and February 2021. A prednisone equivalent threshold of 700 mg defined low (LCD) or high (HCD) cumulative dosing during the 90 days before starting ICIs. At least one 5-day course of ≥ 10 mg prednisone equivalent determined whether the intake was pulse (PCD, ≤ 5 days) or continuous (CCD, &gt; 5 days). Results We included 113 consecutive patients. Durable control benefit and no clinical benefit (NCB) were reported in 53 (47%) and 60 (53%) of the cases, respectively. ECOG PS 1–2, negative PD-L1 expression, HCD, and CCD were significantly related to NCB in multivariate analysis. The median PFS was 4.6 months (95%CI: 3.9–6.3) and median OS was 6.9 months (95% CI: 6.0–8.9) after a median follow-up time of 43.5 months (95% CI: 32.6–54.4). Multivariate analysis of survival confirmed ECOG PS 1–2 ( p  = 0.005), negative PD-L1 expression ( p  = 0.002), and CCD ( p  = 0.001) significantly correlated with an increased risk of mortality. Conclusions These findings imply that immunosuppressive corticosteroid dosing before ICIs, even of short duration, might affect survival. The constraints of this study and lack of reliable comparisons suggest a hypothesis-generating value of these results.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-022-04416-4</identifier><identifier>PMID: 35301584</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adrenal Cortex Hormones - therapeutic use ; B7-H1 Antigen - metabolism ; Cancer Research ; Carcinoma, Non-Small-Cell Lung ; Corticoids ; Corticosteroids ; Disease control ; Dosage ; Equivalence ; Humans ; Immune checkpoint inhibitors ; Immune Checkpoint Inhibitors - adverse effects ; Immunosuppression ; Lung cancer ; Lung Neoplasms ; Medicine ; Medicine &amp; Public Health ; Multivariate analysis ; Non-small cell lung carcinoma ; Observational studies ; Oncology ; Original Article ; Patients ; PD-L1 protein ; Pharmacology/Toxicology ; Prednisone ; Prednisone - therapeutic use ; Progression-Free Survival ; Retrospective Studies ; Small cell lung carcinoma ; Steroids ; Survival</subject><ispartof>Cancer chemotherapy and pharmacology, 2022-04, Vol.89 (4), p.529-537</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>2022. 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R. Giron</creatorcontrib><creatorcontrib>Giannarelli, D.</creatorcontrib><creatorcontrib>Fabbri, A.</creatorcontrib><creatorcontrib>Marrucci, E.</creatorcontrib><creatorcontrib>Ruggeri, E. M.</creatorcontrib><title>Impact of previous corticosteroid exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective observational study</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Background Immunosuppressive dosing of corticosteroids at the start of treatment impairs immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC). Previous cumulative dose and intake modality of corticosteroids may result in different levels of immunosuppression. We sought to determine whether these aspects could predict disease control and survival in NSCLC patients receiving ICIs. Methods We conducted a retrospective single-center study, including patients treated with ICI as second-line therapy at our institution between July 2015 and February 2021. A prednisone equivalent threshold of 700 mg defined low (LCD) or high (HCD) cumulative dosing during the 90 days before starting ICIs. At least one 5-day course of ≥ 10 mg prednisone equivalent determined whether the intake was pulse (PCD, ≤ 5 days) or continuous (CCD, &gt; 5 days). Results We included 113 consecutive patients. Durable control benefit and no clinical benefit (NCB) were reported in 53 (47%) and 60 (53%) of the cases, respectively. ECOG PS 1–2, negative PD-L1 expression, HCD, and CCD were significantly related to NCB in multivariate analysis. The median PFS was 4.6 months (95%CI: 3.9–6.3) and median OS was 6.9 months (95% CI: 6.0–8.9) after a median follow-up time of 43.5 months (95% CI: 32.6–54.4). Multivariate analysis of survival confirmed ECOG PS 1–2 ( p  = 0.005), negative PD-L1 expression ( p  = 0.002), and CCD ( p  = 0.001) significantly correlated with an increased risk of mortality. Conclusions These findings imply that immunosuppressive corticosteroid dosing before ICIs, even of short duration, might affect survival. 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R. Giron</au><au>Giannarelli, D.</au><au>Fabbri, A.</au><au>Marrucci, E.</au><au>Ruggeri, E. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of previous corticosteroid exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective observational study</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>89</volume><issue>4</issue><spage>529</spage><epage>537</epage><pages>529-537</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Background Immunosuppressive dosing of corticosteroids at the start of treatment impairs immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC). Previous cumulative dose and intake modality of corticosteroids may result in different levels of immunosuppression. We sought to determine whether these aspects could predict disease control and survival in NSCLC patients receiving ICIs. Methods We conducted a retrospective single-center study, including patients treated with ICI as second-line therapy at our institution between July 2015 and February 2021. A prednisone equivalent threshold of 700 mg defined low (LCD) or high (HCD) cumulative dosing during the 90 days before starting ICIs. At least one 5-day course of ≥ 10 mg prednisone equivalent determined whether the intake was pulse (PCD, ≤ 5 days) or continuous (CCD, &gt; 5 days). Results We included 113 consecutive patients. Durable control benefit and no clinical benefit (NCB) were reported in 53 (47%) and 60 (53%) of the cases, respectively. ECOG PS 1–2, negative PD-L1 expression, HCD, and CCD were significantly related to NCB in multivariate analysis. The median PFS was 4.6 months (95%CI: 3.9–6.3) and median OS was 6.9 months (95% CI: 6.0–8.9) after a median follow-up time of 43.5 months (95% CI: 32.6–54.4). Multivariate analysis of survival confirmed ECOG PS 1–2 ( p  = 0.005), negative PD-L1 expression ( p  = 0.002), and CCD ( p  = 0.001) significantly correlated with an increased risk of mortality. Conclusions These findings imply that immunosuppressive corticosteroid dosing before ICIs, even of short duration, might affect survival. The constraints of this study and lack of reliable comparisons suggest a hypothesis-generating value of these results.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>35301584</pmid><doi>10.1007/s00280-022-04416-4</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8374-1362</orcidid></addata></record>
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subjects Adrenal Cortex Hormones - therapeutic use
B7-H1 Antigen - metabolism
Cancer Research
Carcinoma, Non-Small-Cell Lung
Corticoids
Corticosteroids
Disease control
Dosage
Equivalence
Humans
Immune checkpoint inhibitors
Immune Checkpoint Inhibitors - adverse effects
Immunosuppression
Lung cancer
Lung Neoplasms
Medicine
Medicine & Public Health
Multivariate analysis
Non-small cell lung carcinoma
Observational studies
Oncology
Original Article
Patients
PD-L1 protein
Pharmacology/Toxicology
Prednisone
Prednisone - therapeutic use
Progression-Free Survival
Retrospective Studies
Small cell lung carcinoma
Steroids
Survival
title Impact of previous corticosteroid exposure on outcomes of patients receiving immune checkpoint inhibitors for advanced non-small cell lung cancer: a retrospective observational study
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