Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer
Background: Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/23/5502 |
| _version_ | 1797400364197085184 |
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| author | George Raynes Mark Stares Samantha Low Dhania Haron Hussain Sarwar Dhruv Abhi Colin Barrie Barry Laird Caledonian Cachexia Collaborative Iain Phillips Melanie MacKean |
| author_facet | George Raynes Mark Stares Samantha Low Dhania Haron Hussain Sarwar Dhruv Abhi Colin Barrie Barry Laird Caledonian Cachexia Collaborative Iain Phillips Melanie MacKean |
| author_sort | George Raynes |
| collection | DOAJ |
| description | Background: Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessation. Interestingly, patients experiencing irAEs demonstrate better survival outcomes. Biomarkers of systemic inflammation, including the Scottish Inflammatory Prognostic Score (SIPS), also predict survival in this patient group. This study examines the relationship between inflammatory status, irAEs, and survival outcomes in NSCLC. Methods: A retrospective analysis was conducted on patients with NSCLC expressing PD-L1 ≥ 50% receiving first-line pembrolizumab monotherapy at a large cancer centre in Scotland. Regression analyses were conducted to examine the relationship between SIPS, irAEs, and survival. Results: 83/262 eligible patients (32%) experienced an irAE. Dermatological, endocrine, gastrointestinal, and hepatic, but not pulmonary, irAEs were associated with prolonged PFS and OS (<i>p</i> <= 0.011). Mild irAEs were associated with better PFS and OS in all patients, including on time-dependent analyses (HR0.61 [95% CI 0.41–0.90], <i>p</i> = 0.014 and HR0.41 [95% CI 0.26–0.63], <i>p</i> < 0.001, respectively). SIPS predicted PFS (HR 1.60 [95% CI 1.34–1.90], <i>p</i> < 0.001) and OS (HR 1.69 [95% CI 1.41–2.02], <i>p</i> < 0.001). SIPS predicted the occurrence of any irAE in all patients (<i>p</i> = 0.011), but not on 24-week landmark analyses (<i>p</i> = 0.174). The occurrence of irAEs predicted favourable outcomes regardless of the baseline inflammatory status (<i>p</i> = 0.015). Conclusion: The occurrence of certain irAEs is associated with a survival benefit in patients with NSCLC expressing PD-L1 ≥ 50% receiving pembrolizumab. We find that the association between low levels of systemic inflammation and the risk of irAEs is confounded by their independent prognostic value. |
| first_indexed | 2024-03-09T01:54:31Z |
| format | Article |
| id | doaj.art-1e18a07532cc42d5abbea98892650fe6 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T01:54:31Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1e18a07532cc42d5abbea98892650fe62023-12-08T15:12:21ZengMDPI AGCancers2072-66942023-11-011523550210.3390/cancers15235502Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung CancerGeorge Raynes0Mark Stares1Samantha Low2Dhania Haron3Hussain Sarwar4Dhruv Abhi5Colin Barrie6Barry Laird7Caledonian Cachexia CollaborativeIain Phillips8Melanie MacKean9Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKCancer Research UK Scotland Centre, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKEdinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UKBackground: Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessation. Interestingly, patients experiencing irAEs demonstrate better survival outcomes. Biomarkers of systemic inflammation, including the Scottish Inflammatory Prognostic Score (SIPS), also predict survival in this patient group. This study examines the relationship between inflammatory status, irAEs, and survival outcomes in NSCLC. Methods: A retrospective analysis was conducted on patients with NSCLC expressing PD-L1 ≥ 50% receiving first-line pembrolizumab monotherapy at a large cancer centre in Scotland. Regression analyses were conducted to examine the relationship between SIPS, irAEs, and survival. Results: 83/262 eligible patients (32%) experienced an irAE. Dermatological, endocrine, gastrointestinal, and hepatic, but not pulmonary, irAEs were associated with prolonged PFS and OS (<i>p</i> <= 0.011). Mild irAEs were associated with better PFS and OS in all patients, including on time-dependent analyses (HR0.61 [95% CI 0.41–0.90], <i>p</i> = 0.014 and HR0.41 [95% CI 0.26–0.63], <i>p</i> < 0.001, respectively). SIPS predicted PFS (HR 1.60 [95% CI 1.34–1.90], <i>p</i> < 0.001) and OS (HR 1.69 [95% CI 1.41–2.02], <i>p</i> < 0.001). SIPS predicted the occurrence of any irAE in all patients (<i>p</i> = 0.011), but not on 24-week landmark analyses (<i>p</i> = 0.174). The occurrence of irAEs predicted favourable outcomes regardless of the baseline inflammatory status (<i>p</i> = 0.015). Conclusion: The occurrence of certain irAEs is associated with a survival benefit in patients with NSCLC expressing PD-L1 ≥ 50% receiving pembrolizumab. We find that the association between low levels of systemic inflammation and the risk of irAEs is confounded by their independent prognostic value.https://www.mdpi.com/2072-6694/15/23/5502biomarkers of systemic inflammationScottish Inflammatory Prognostic Score (SIPS)non-small-cell lung cancerimmune-related adverse eventspembrolizumab |
| spellingShingle | George Raynes Mark Stares Samantha Low Dhania Haron Hussain Sarwar Dhruv Abhi Colin Barrie Barry Laird Caledonian Cachexia Collaborative Iain Phillips Melanie MacKean Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer Cancers biomarkers of systemic inflammation Scottish Inflammatory Prognostic Score (SIPS) non-small-cell lung cancer immune-related adverse events pembrolizumab |
| title | Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer |
| title_full | Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer |
| title_fullStr | Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer |
| title_full_unstemmed | Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer |
| title_short | Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer |
| title_sort | immune related adverse events biomarkers of systemic inflammation and survival outcomes in patients receiving pembrolizumab for non small cell lung cancer |
| topic | biomarkers of systemic inflammation Scottish Inflammatory Prognostic Score (SIPS) non-small-cell lung cancer immune-related adverse events pembrolizumab |
| url | https://www.mdpi.com/2072-6694/15/23/5502 |
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