Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis
Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or com...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6063 |
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| author | Maria Gemelli Diego Luigi Cortinovis Alice Baggi Pierluigi di Mauro Stefano Calza Alfredo Berruti Salvatore Grisanti Matteo Rota |
| author_facet | Maria Gemelli Diego Luigi Cortinovis Alice Baggi Pierluigi di Mauro Stefano Calza Alfredo Berruti Salvatore Grisanti Matteo Rota |
| author_sort | Maria Gemelli |
| collection | DOAJ |
| description | Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (<i>p</i> < 0.001 and <i>p</i> = 0.006, respectively) or anti CTLA-4 (<i>p</i> < 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13–27%) and 56% (95% CI 45–67%), respectively, and they did not significantly differ between combined and single agent treatments (<i>p</i> = 0.088 and <i>p</i> = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (<i>p</i> = 0.0545 and <i>p</i> = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (<i>p</i> = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted. |
| first_indexed | 2024-03-09T17:14:40Z |
| format | Article |
| id | doaj.art-bc12b77dfff6472386368c4606dea163 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:14:40Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bc12b77dfff6472386368c4606dea1632023-11-24T13:45:34ZengMDPI AGCancers2072-66942022-12-011424606310.3390/cancers14246063Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-AnalysisMaria Gemelli0Diego Luigi Cortinovis1Alice Baggi2Pierluigi di Mauro3Stefano Calza4Alfredo Berruti5Salvatore Grisanti6Matteo Rota7Medical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica, 20099 Milan, ItalyDepartment of Medical Oncology-ASST-Monza Ospedale San Gerardo, 20900 Monza, ItalyDepartment of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, ItalyUnit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, ItalyDepartment of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, 25123 Brescia, ItalyUnit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, ItalyMany clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (<i>p</i> < 0.001 and <i>p</i> = 0.006, respectively) or anti CTLA-4 (<i>p</i> < 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13–27%) and 56% (95% CI 45–67%), respectively, and they did not significantly differ between combined and single agent treatments (<i>p</i> = 0.088 and <i>p</i> = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (<i>p</i> = 0.0545 and <i>p</i> = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (<i>p</i> = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted.https://www.mdpi.com/2072-6694/14/24/6063pleural mesotheliomaimmune checkpoint inhibitorsimmunotherapyanti PD-1/PD-L1anti CTLA-4 |
| spellingShingle | Maria Gemelli Diego Luigi Cortinovis Alice Baggi Pierluigi di Mauro Stefano Calza Alfredo Berruti Salvatore Grisanti Matteo Rota Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis Cancers pleural mesothelioma immune checkpoint inhibitors immunotherapy anti PD-1/PD-L1 anti CTLA-4 |
| title | Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis |
| title_full | Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis |
| title_fullStr | Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis |
| title_full_unstemmed | Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis |
| title_short | Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis |
| title_sort | immune checkpoint inhibitors in malignant pleural mesothelioma a systematic review and meta analysis |
| topic | pleural mesothelioma immune checkpoint inhibitors immunotherapy anti PD-1/PD-L1 anti CTLA-4 |
| url | https://www.mdpi.com/2072-6694/14/24/6063 |
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