A systematic review and meta-analysis of trials assessing PD-1/PD-L1 immune checkpoint inhibitors activity in pre-treated advanced stage malignant mesothelioma

Tagliamento, Marco; Bironzo, Paolo; Curcio, H.; Luca, Emmanuele De; Pignataro, Daniele; Rapetti, Simonetta Grazia; Audisio, Marco; Bertaglia, Valentina; Paratore, C.; Bungaro, Maristella; Olmetto, Emanuela; Artusio, Elisa; Reale, Maria Lucia; Zichi, Clizia; Capelletto, Enrica; Carnio, Simona; Buffoni, L; Passiglia, Francesco; Novello, Silvia; Scagliotti, Giorgio Vittorio; Maïo, Massimo Di

doi:10.1016/j.critrevonc.2022.103639

Cited by 18 publications

(8 citation statements)

References 45 publications

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“…Our data showed that PD-L1-positive patients have higher probability of response or achieving disease control with ICI treatment than PD-L1-negative patients, considering 1% of expression as cut-off for positivity. This is in line with what was reported by Tagliamento et al [ 43 ]. However, the role of PD-L1 tumor expression is still debated.…”

Section: Discussionsupporting

confidence: 94%

“…Interestingly, in the second-line setting, single-agent anti-PD-1/PD-L1 had a 17% ORR and a 55% DCR, which are slightly higher than the historical data for “standard” second-line chemotherapy (gemcitabine/vinorelbine) and do not significantly differ from the combination treatment (21% ORR and 60% DCR, respectively). This is in line with what has been reported in another meta-analysis by Tagliamento et al on 13 studies including 888 pre-treated patients, in which the ORR and DCR were 18.1% (95% confidence interval [CI] 13.9–22.8%) and 55.4% (95% CI: 48.1–62.5%), respectively, whereas the median PFS ranged from 2.1 to 5.9 and the OS from 6.7 to 20.9 months [ 43 ]. Moreover, also considering other experimental treatments, such as the combination of chemotherapy and antiangiogenics, single-agent anti-PD1 inhibitors can confer benefit for pre-treated patients with PM, with a favorable toxicity profile, as revealed in another meta-analysis by Banna et al [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

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Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Gemelli

Cortinovis

Baggi

et al. 2022

Cancers

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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 (p < 0.001 and p = 0.006, respectively) or anti CTLA-4 (p < 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 (p = 0.088 and p = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (p = 0.0545 and p = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (p = 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.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Gemelli

Cortinovis

Baggi

et al. 2022

Cancers

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“…Two recent meta-analyses indicate a possible opportunity for this ‘orphan drug’ population even if ICI predictive factors may be claimed to increase the risk–benefit ratio of this therapeutic solution. 24 , 25 …”

Section: Discussionmentioning

confidence: 99%

Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma

Cortinovis¹,

Canova²,

Colonese³

et al. 2022

ESMO Open

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“…The authors concluded that anti-PD-(L)1 ICIs can be considered a treatment option in MPM progressing after chemotherapy, even in the absence of identified predictive response factors. 60 …”

Section: Treatment Of Mpm With Cpis After Failure Of Other Therapies ...mentioning

confidence: 99%

Advances in Immunotherapy for Malignant Pleural Mesothelioma: From Emerging Strategies to Translational Insights

López-Castro,

Fuentes-Martín,

Medina del Valle

et al. 2024

Open Respiratory Archives

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A systematic review and meta-analysis of trials assessing PD-1/PD-L1 immune checkpoint inhibitors activity in pre-treated advanced stage malignant mesothelioma

Cited by 18 publications

References 45 publications

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma

Advances in Immunotherapy for Malignant Pleural Mesothelioma: From Emerging Strategies to Translational Insights

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